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Purpose: To determine predictive factors of higher levels of best-corrected visual acuity (BCVA) in the long-term after primary Descemet's membrane endothelial keratoplasty (DMEK)., Methods: Retrospective, single-surgeon case series of 129 successful primary DMEK eyes without graft failure and with a minimum postoperative follow-up of 12 months. Mixed effect model for repeated measurements (MMRM) analysis was performed to determine recipient, donor, surgical and postoperative factors associated with BCVA ≤ 0.10 logMAR (≥ 20/25 Snellen)., Results: After primary DMEK, there was a statistically significant improvement in BCVA with a global reduction in logMAR BCVA (p < 0.00001). There was also a global tendency towards increasing proportion of eyes with BCVA ≤ 0.10 logMAR at all time points (p < 0.00001), from 1.6% before DMEK to 64.4% in eyes with more than 5 years of F-U. Absence of retinal disease was associated with a decrease of 0.10 logMAR in postoperative BCVA after primary DMEK, maintaining constant the rest of variables (p < 0.001). The variables age (OR 0.960), postoperative time (OR 1.083), preoperative BCVA ≥ 0.375 logMAR (OR 0.162) and indication for DMEK (OR 5.412) were included in the predictive MMRM model of BCVA ≤ 0.10 logMAR., Conclusion: Primary DMEK is associated with statistically and clinically significant improvement in BCVA that occur early in the postoperative period and are continuous over time. Eyes with retinal comorbidities have increased risk of worse postoperative BCVA after DMEK. Younger recipient age, Fuchs' dystrophy eyes and eyes with better preoperative BCVA are more likely to achieve postoperative BCVA ≤ 0.10 logMAR., Competing Interests: Declarations Conflict of interest The authors declare no conflict of interests. Research involving human participants This retrospective chart review study involving human participants was in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This study was approved by an institutional review board (IRB)—Comisión de Ética e Investigación Médica del Instituto de Microcirugía Ocular—CEIm, study COD IMO 210324-174., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: Corneal neurotization is an emerging technique that offers potential for visual rehabilitation in neurotrophic keratopathy. This study reports on a multicenter experience and outcomes for both direct and indirect methods of corneal neurotization., Methods: Retrospective case series. Sixteen patients with neurotrophic keratopathy who underwent corneal neurotization across 5 centers in Australia and Israel were identified for inclusion. Corneal neurotization was performed via direct neurotization from the ipsilateral or contralateral supraorbital/supratrochlear nerve or by the use of an interpositional sural nerve graft. Change in corneal sensitivity (measured in millimeters by the Cochet-Bonnet aesthesiometer), visual acuity, and corneal health., Results: Over a mean follow-up period of 31.3 months (range: 3 months-8 years), mean corneal sensitivity improved from 3.6 mm (range: 0-25 mm) to 25.3 mm (range: 0-57 mm). Visual acuity improved on average from 20/380 to 20/260. Twelve of 16 patients (75.0%) improved in at least 2 out of the 3 main outcome measures. Nine patients (56.3%) showed an improvement in visual acuity; 13 (81.3%) showed an improvement in average corneal sensitivity; and 11 (68.8%) showed an improvement in corneal health. There were no intraoperative or postoperative complications., Conclusions: Corneal neurotization is an emerging surgical treatment option for the management of neurotrophic keratopathy. With appropriate case selection, outcomes are favorable and complication rates are low, for a condition that is otherwise challenging to manage. Patients with severe neurotrophic keratopathy should be considered for this surgical treatment option., Competing Interests: The authors have no financial or conflicts of interest to disclose., (Copyright © 2024 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

Purpose: To investigate whether neurotrophic keratopathy is present in limbal stem cell deficiency (LSCD), by measuring corneal sensation and characterizing corneal subbasal nerve plexus., Design: Prospective, cross-sectional, case-control comparative study., Methods: A total of 46 eyes with LSCD and 14 normal eyes were recruited from 2019 to 2022. Corneal sensation was measured using a Cochet-Bonnet esthesiometer, and subbasal nerve plexus was imaged using in vivo confocal microscopy (IVCM) at the central cornea and 4 limbal regions. Subbasal nerve density (SND, number of nerves/mm 2 ), subbasal nerve length (SNL, total length of nerves/mm 2 ) and subbasal nerve branch density (SNBD, number of branches/mm 2 ) were quantified. LSCD was graded to stage 1, 2, and 3 using a previously established staging method consisting of clinical scores, basal cell density, central corneal epithelial thickness, and SNL., Results: The mean (±SD) cornea sensation in the central cornea and limbus were 29.2 ± 21.5 and 33.6 ± 15.1 mm in the LSCD group and 57.6 ± 5.8 and 54.3 ± 4.7 mm in the control group, respectively (all P < .001). In sectoral LSCD, the corneal sensation in the affected regions (29.1 ± 17.6 mm) decreased significantly compared to the unaffected regions (41.4 ± 18.2 mm, P < .001). Central corneal SND, SNL, and SNBD were reduced by 84.6%, 82.6%, and 89.2%, respectively, in LSCD compared to controls (all P < 0.05). The central corneal sensation negatively correlated with the severity of LSCD (rho = -0.64, P < .0001) and positively correlated with SND, SNL, and SNBD (rho = 0.63, 0.66, and 0.56, respectively; all P < .001)., Conclusions: Corneal sensation was reduced in eyes with LSCD. The degree of corneal sensation reduction positively correlated with the severity of LSCD. This finding demonstrated the coexistence of neurotropic keratopathy in LSCD., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Descemet membrane endothelial keratoplasty (DMEK) has become the dominant keratoplasty procedure. However, the impact of high intraocular pressure (IOP) on the DMEK prognosis in patients without preexisting glaucoma remains unknown., Methods: Non-glaucoma patients who underwent DMEK in Peking University Third Hospital between July 2017 and March 2023 with a follow-up duration longer than six months were included in this cohort study. Eyes were divided into three groups: Group A) normal IOP; Group B) early IOP elevation (IOP ≥ 30 mmHg or increase of more than 10 mmHg from baseline within 3 days); Group C) intermediate-term IOP elevation (IOP > 21 mmHg or increase of more than 10 mmHg from baseline after 14 days postoperatively). The postoperative IOP, endothelial cell density (ECD), central corneal thickness (CCT), best-corrected visual acuity (BCVA) and rate of graft failure were analysed., Results: Forty-seven eyes from forty-seven patients were included. Thirty-seven eyes were bullous keratopathy, and ten were Fuchs endothelial corneal dystrophy. Twenty-five eyes were classified as Group A, six as Group B and sixteen as Group C. The mean peak IOP was 49.00 ± 4.99 mmHg in Group B eyes and 31.89 ± 11.75 mmHg in Group C eyes. The postoperative BCVA significantly differed from that before surgery (P < 0.001). The ECD at 3 months after surgery in eyes with intermediate-term IOP elevation was lower (P = 0.032). Four eyes with intermediate-term IOP elevation developed graft failure (P = 0.001)., Conclusions: Intermediate-term IOP elevation after DMEK may reduce the graft ECD and lead to graft failure within six months after surgery. However, early IOP elevation had no effect on the prognosis. Careful IOP monitoring and intermediate-term IOP management should be conducted for graft protection., (© 2024. The Author(s).)

Purpose: The aim of this study was to report long-term follow-up of eyes undergoing Descemet stripping only (DSO)., Methods: This was a retrospective study including 26 eyes of 20 patients undergoing DSO between December 2015 and November 2022. Eligibility criteria included peripheral endothelial cell count (ECC) >1000 cells/mm 2 and symptoms caused by central guttata. Patients underwent a central circular 4-mm descemetorhexis using a reverse Sinskey hook and a pair of descemetorhexis forceps using a peeling technique. Three parameters were measured before surgery and at last follow-up: best-corrected visual acuity (BCVA), central corneal thickness (CCT), and ECC measured centrally and at the periphery., Results: The mean age was 73 ± 9 years [52-90 years]. The average follow-up period was 23.7 ± 24.8 months [3-84]. Twenty-two eyes responded to DSO with 20 female eyes (91%) and 2 male eyes (9%). The mean postoperative BCVA improved from 0.3 ± 0.17 logMAR to 0.09 ± 0.13 logMAR ( P value <0.05). The mean postoperative CCT decreased from 588 ± 41 μm to 546 ± 50 μm ( P -value <0.05). The mean postoperative central ECC was 780 ± 257 cells/mm 2 [484-1500]. Peripheral ECC decreased postoperatively (1837 ± 407 cells/mm 2 preoperatively to 864 ± 340 cells/mm 2 postoperatively, P value >0.05). Peripheral endothelial cell polymegathism was stable (average of 26.8% ± 6.8% preoperatively and 30.2% ± 14% postoperatively). Average peripheral endothelial cells polymorphism decreased postoperatively (63.1 ± 20.5% preoperatively to 33% ± 25% postoperatively, P value >0.05). Four eyes did not show improvement after DSO and underwent Descemet membrane endothelial keratoplasty surgery. There were 3 men (75%) and 1 women (25%). The preoperative trend was for nonresponders to have lower BCVA, higher CCT, more abnormal peripheral polymorphism, and polymegathism., Conclusions: The results of this study, with up to 7 years follow up, demonstrate the durability of DSO., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: To evaluate the efficacy and safety of trans-epithelial phototherapeutic keratectomy (TE-PTK) as a treatment for recurrent corneal erosion syndrome (RCES) in patients with symptoms refractory to conventional treatments., Methods: All patients who received TE-PTK treatment for RCES had failed 3 or more conventional treatments and were reviewed, and if met criteria, approved by healthcare workers of the British Columbia public health authority (Medical Services Plan (MSP). A retrospective chart review and telephone survey were conducted at the Pacific Laser Eye Centre (PLEC). Exclusion criteria were ocular co-morbidities potentially affecting treatment efficacy., Results: This study included 593 eyes of 555 patients (46.2% male; 50.9 ± 14.2 years old) who underwent TE-PTK. The leading identified causes of RCES were trauma (45.7%) and anterior basement membrane dystrophy (44.2%). The most common pre-PTK interventions were ocular lubricants (90.9%), hypertonic solutions (77.9%), and bandage contact lenses (50.9%). Thirty-six eyes had undergone surgical interventions such as stromal puncture, epithelial debridement, or diamond burr polishing. Post-PTK, 78% of patients did not require any subsequent therapies and 20% required ongoing drops. Six patients (1.1%) reported no symptom improvement and required repeat TE-PTK for ongoing RCES symptoms after initial TE-PTK. All 6 eyes were successfully retreated with TE-PTK (average time to retreatment was 11.3 ± 14.9 months). There was no significant difference in best corrected visual acuity pre- vs. post-operatively. The mean post-operative follow-up was 60.5 months (range: 5-127 months)., Conclusion: TE-PTK has a good efficacy and safety profile for treatment-resistant RCES. The third-party public health-reviewed nature of this study, the low recurrence rate of RCES, and the low PTK retreatment rate suggest that TE-PTK might be considered for wider use in the management of RCES., (© 2024. The Author(s).)

Neurotrophic keratopathy is an uncommon degenerative corneal disorder characterized by compromised corneal sensory innervation resulting in the formation of epithelial defects and nonhealing corneal ulcers. Various treatment modalities are available to stabilize disease progression, improve patient well-being, and prevent vision loss. For eligible patients, medical and surgical reinnervation have emerged as pioneering therapies, holding promise for better management. We present a comprehensive review of the disorder, providing an update relevant to ophthalmologists on pathogenesis, diagnosis, treatment options, and novel therapies targeting pathophysiological pathways., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: This study aimed to investigate the long-term effects of COVID-19 on corneal endothelial cell morphology in patients with ocular symptoms to assess possible corneal involvement in patients who recovered., Methods: The COVID-19 group included patients diagnosed and treated at Istanbul University Cerrahpasa Medical Faculty with confirmed SARS-CoV-2 infection and ocular irritation symptoms. The control group was comprised of age- and sex-matched individuals. The controls had no ocular pathologies. Noncontact specular microscopy (Konan Cell Check SL, Hyogo, Japan) was performed using the center method after 156 ± 16 days of COVID-19 diagnosis. Parameters such as endothelial cell density (ECD), hexagonality (HEX), coefficient of variation, and central corneal thickness were analyzed., Results: Specular microscopy results of 54 COVID-19 patients with ocular irritation symptoms and 72 controls were evaluated. Ocular symptoms in COVID-19 patients included conjunctival hyperemia, foreign body sensation, tearing, ocular secretion, and chemosis. Mean (±SD) ECD was 2770 ± 31 (cells/mm 2 ) in the COVID-19 group and 2897 ± 26 in the control group, and mean (±SD) HEX was 46.52 ± 6.38 in the COVID-19 group and 58.22 ± 13.94 in the control group. COVID-19 patients exhibited significantly lower endothelial ECD and HEX levels than controls ( P = 0.003 and P < 0.001, respectively). Coefficient of variation and central corneal thickness analyses did not reach statistical significance., Conclusions: COVID-19 can cause long-term alterations in the corneal endothelial cells, leading to decreased ECD and HEX. Future research should focus on the long-term implications of COVID-19 on the corneal health and visual outcomes., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To study the outcome of eyes that underwent surgery for keratoprosthesis with a biological haptic, osteo-odonto-keratoprosthesis (OOKP) or tibia keratoprosthesis, by a single surgeon over a time span of more than 25 years., Methods: One hundred thirty eyes that had received a keratoprosthesis with a biological haptic between 1994 and 2022 by a single surgeon were included in this retrospective analysis. Main outcome parameters were postoperative best corrected visual acuity, postoperative refractive error, postoperative complications, anatomical and functional survival of the prosthesis as well as comparison of subgroups of the 2 different types (OOKP n = 78; tibia keratoprosthesis n = 52) of keratoprostheses, and subgroup analysis of different indications for surgery. Patients were examined every 6 months., Results: The longest follow-up was 25.8 years. Reasons for implantation were graft-vs-host disease (6.9%), vascularized corneas and dry eye (22.9%), physical or chemical burns (29.8%), Stevens-Johnson syndrome (9.9%), and ocular cicatricial pemphigoid (30.5%). The functional success rate with postoperative visual acuity of better than 0.7 log MAR was achieved by 56.9%. The OOKP subgroup showed a better mean visual outcome. 14 keratoprostheses (10.7%) had to be explanted over the whole time span. In the time leading to explantation, refraction showed a statistically significant myopic shift when compared with the non-explanted prosthesis. Anatomical survival rates were better for the OOKP in the first 12 years after implantation., Conclusions: The study shows that keratoprosthesis with a biological haptic has favorable long-term outcomes. The retention rate stayed very high with excellent functional outcomes., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To review the published literature on the safety and outcomes of keratolimbal allograft (KLAL) transplantation and living-related conjunctival limbal allograft (lr-CLAL) transplantation for bilateral severe/total limbal stem cell deficiency (LSCD)., Methods: Literature searches were last conducted in the PubMed database in February 2023 and were limited to the English language. They yielded 523 citations; 76 were reviewed in full text, and 21 met the inclusion criteria. Two studies were rated level II, and the remaining 19 studies were rated level III. There were no level I studies., Results: After KLAL surgery, best-corrected visual acuity (BCVA) improved in 42% to 92% of eyes at final follow-up (range, 12-95 months). The BCVA was unchanged in 17% to 39% of eyes and decreased in 8% to 29% of eyes. Two of 14 studies that evaluated the results of KLAL reported a notable decline in visual acuity over time postoperatively. Survival of KLAL was variable, ranging from 21% to 90% at last follow-up (range, 12-95 months) and decreased over time. For patients undergoing lr-CLAL surgery, BCVA improved in 31% to 100% of eyes at final follow-up (range, 16-49 months). Of the 9 studies evaluating lr-CLAL, 4 reported BCVA unchanged in 30% to 39% of patients, and 3 reported a decline in BCVA in 8% to 10% of patients. The survival rate of lr-CLAL ranged from 50% to 100% at final follow-up (range, 16-49 months). The most common complications were postoperative elevation of intraocular pressure, persistent epithelial defects, and acute allograft immune rejections., Conclusions: Given limited options for patients with bilateral LSCD, both KLAL and lr-CLAL are viable choices that may provide improvement of vision and ocular surface findings. The studies trend toward a lower rejection rate and graft failure with lr-CLAL. However, the level and duration of immunosuppression vary widely between the studies and may impact allograft rejections and long-term graft survival. Complications related to immunosuppression are minimal. Repeat surgery may be needed to maintain a viable ocular surface. Reasonable long-term success can be achieved with both KLAL and lr-CLAL with appropriate systemic immunosuppression., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the tear proteomic and neuromediator profiles, in vivo confocal microscopy (IVCM) imaging features, and clinical manifestations in neuropathic corneal pain (NCP) patients., Design: Cross-sectional study., Methods: A total of 20 NCP patients and 20 age-matched controls were recruited. All subjects were evaluated by corneal sensitivity, Schirmer test, tear break-up time, and corneal and ocular surface staining, Ocular Surface Disease Index and Ocular Pain Assessment Survey questionnaires were administered, as well as IVCM examinations for corneal nerves, microneruomas, and epithelial and dendritic cells. Tears were collected for neuromediator and proteomic analysis using enzyme-linked immunosorbent assay and data-independent acquisition mass spectrometry., Results: Burning and sensitivity to light were the 2 most common symptoms in NCP. A total of 188 significantly dysregulated proteins, such as elevated metallothionein-2, creatine kinases B-type, vesicle-associated membrane protein 2, neurofilament light polypeptide, and myelin basic protein, were identified in the NCP patients. The top 10 dysregulated biological pathways in NCP include neurotoxicity, axonal signaling, wound healing, neutrophil degradation, apoptosis, thrombin signaling mitochondrial dysfunction, and RHOGDI and P70S6K signaling pathways. Compared to controls, the NCP cohort presented with significantly decreased corneal sensitivity (P < .001), decreased corneal nerve fiber length (P = .003), corneal nerve fiber density (P = .006), and nerve fiber fractal dimension (P = .033), as well as increased corneal nerve fiber width (P = .002), increased length, total area and perimeter of microneuromas (P < .001, P < .001, P = .019), smaller corneal epithelial size (P = .017), and higher nerve growth factor level in tears (P = .006)., Conclusions: These clinical manifestations, imaging features, and molecular characterizations would contribute to the diagnostics and potential therapeutic targets for NCP., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to describe a new surgical technique for deep anterior lamellar keratoplasty., Methods: All pupils in the recipient eyes were dilated preoperatively. Vertical grooving was performed using a crescent blade with a width of 5 mm and a depth of one-third to half corneal thickness on the temporal side of the limbus. Stromal dissection was performed as close as possible to Descemet membrane by observing the gap between the gold line by retinal reflex and the front edge of the crescent blade. Lamellar dissection was performed along the lamellar plane using corneal dissectors. The ophthalmic viscoelastic device was injected into the intrastromal pocket to separate the anterior and posterior stroma and an anterior corneal lamella was excised. A donor cornea was sutured into the recipient bed., Results: In 18 eyes, none of the patients had Descemet membrane rupture during surgery. The mean postoperative residual stromal thickness was 80 ± 31 μm. The mean central corneal thickness after surgery was 660 ± 69 μm. At the last follow-up, the cornea was cleared in all 18 eyes on slit-lamp examination., Conclusions: We estimated the residual stromal thickness based on the gap between the gold line by the retinal reflex and crescent blade, and intrastromal lamellar dissection was performed using a smooth corneal dissector. Consequently, the surface of stromal dissection was smooth, and the residual stromal thickness was even., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: The purpose of this study was to describe a method to achieve a high success rate for nanothin (NT, ≤50 μm) Descemet stripping automated endothelial keratoplasty (DSAEK) graft preparation using anterior chamber pressurizer (ACP) with a modified setting and evaluate its postoperative efficacy., Methods: A prospective cohort (study group) of 24 patients with corneal endothelial dysfunction was consecutively enrolled and received DSAEK grafts using the modified ACP method from December 2021 to May 2022. The control group included 24 historical patients who received DSAEK grafts using conventional ACP procedure. Central graft thickness (CGT), graft regularity (3-mm and 5-mm diameter zones), best spectacle-corrected visual acuity, and endothelial cell density (ECD) were compared between 2 groups., Results: A 100% ultrathin (UT, ≤100 μm) DSAEK rate and 62.5% NT-DSAEK rate was achieved at 3 months postsurgery in the study group, with a 51.3 ± 14.8 μm CGT, while a 70.8% UT-DSAEK rate and 4.2% NT-DSAEK rate was achieved in the control group, with an 89.0 ± 15.4 μm CGT ( P <0.001). At 3-month postoperative follow-up, the regularity of graft thickness was significantly better in the study group (central-to-peripheral thickness difference: P = 0.044 and 0.014 for 3-mm and 5-mm diameter zones, respectively, graft thickness uniformity: P <0.001 and 0.012, respectively). There was no statistical difference in the best spectacle-corrected visual acuity ( P = 0.170) or ECD ( P = 0.833) between 2 groups at 3-month postoperative follow-up., Conclusions: DSAEK grafts harvested using modified ACP method were thinner and more regular compared with the conventional ACP method., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To describe clinical characteristics and visual outcomes of eyes developing neurotrophic keratopathy (NK) following rhegmatogenous retinal detachment (RRD) repair., Methods: All eyes with NK at Wills Eye Hospital following RRD repair from June 1, 2011, to December 1, 2020 were included. Patients with prior ocular procedures (other than cataract surgery), herpetic keratitis, and diabetes mellitus were excluded., Results: During the study period, 241 patients were diagnosed with NK, and 8179 eyes underwent RRD surgery, giving a 9-year prevalence rate of 0.1% (95% CI, 0.1%-0.2%). Mean age was 53.4 ± 16.6 years during RRD repair and 56.5 ± 13.4 years during NK diagnosis. Mean time to NK diagnosis was 3.0 ± 5.6 years (range, 6 days to 18.8 years). Mean visual acuity before NK was 1.10 ± 0.56 logMAR (20/252 Snellen), and it was 1.01 ± 0.62 logMAR (20/205 Snellen) at final visit (p = 0.75). Six eyes (54.5%) developed NK <1 year following RRD surgery. Mean final visual acuity was 1.01 ± 0.53 logMAR (20/205 Snellen) in this group versus 1.01 ± 0.78 logMAR (20/205 Snellen) in the delayed NK group (p = 1.00)., Conclusions: NK may present acutely or up to several years following surgery, with severity of corneal defects ranging from stage 1 to stage 3 NK. Surgeons should be mindful of the potential for this rare complication following RRD repair., (Copyright © 2023 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Corneal neuropathic pain (CNP) is a poorly defined disease entity characterised by an aberrant pain response to normally non-painful stimuli and categorised into having peripheral and central mechanisms, with the former responding to instillation of topical anaesthetic. CNP is a challenging condition to diagnose due to numerous aetiologies, an absence of clinical signs and ancillary tests (in vivo confocal microscopy and esthesiometry), lacking the ability to confirm the diagnosis and having limited availability. Symptomatology maybe mirrored by severe and chronic forms of dry eye disease (DED), often leading to misdiagnosis and inadequate treatment. In practice, patients with suspected CNP can be assessed with questionnaires to elicit symptoms. A thorough ocular assessment is also performed to exclude any co-existent ocular conditions. A medical and mental health history should be sought due to associations with autoimmune disease, chronic pain syndromes, anxiety and depression. Management begins with communicating to the patient the nature of their condition. Ophthalmologists can prescribe topical therapies such as autologous serum eyedrops to optimise the ocular surface and promote neural regeneration. However, a multi-disciplinary treatment approach is often required, including mental health support, particularly when there are central mechanisms. General practitioners, pain specialists, neurologists and psychologists may be needed to assist with oral and behavioural therapies. Less data is available to support the safety and efficacy of adjuvant and surgical therapies and the long-term natural history remains to be determined. Hence clinical trials and registry studies are urgently needed to fill these data gaps with the aim to improve patient care., (© 2024. The Author(s).)

Various corneal diseases are strongly associated with corneal biomechanical characteristics, and early measurement of patients' corneal biomechanics can be utilized in their diagnosis and treatment. Measurement methods for corneal biomechanical characteristics are classified into ex vivo and in vivo. Some of these methods can directly measure certain corneal biomechanical parameters, while others require indirect calculation through alternative methods. However, due to diversities in measurement techniques and environmental conditions, significant differences may exist in the corneal mechanical properties measured by these two methods. Therefore, comprehensive research on current measurement methods and the exploration of novel measurement techniques may have great clinical significance. The corneal elastic modulus, a critical indicator in corneal biomechanics, reflects the cornea's ability to return to its initial shape after undergoing stress. This review aims to provide a comprehensive summary of the corneal elastic modulus, which is a critical biomechanical parameter, and discuss its direct, indirect, and potential measurement methods and clinical applications., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: The aim of this study was to describe the importance of symblepharon release with ocular surface reconstruction (OSR) for optimal fitting of scleral contact lenses (SCLs) in eyes with chronic cicatrizing conjunctivitis (CCC) and keratopathy., Methods: This retrospective study included 32 eyes with CCC and keratopathy with symblepharon which underwent symblepharon release with OSR and were fitted with SCLs. The primary outcome measure was the improvement in best-corrected visual acuity with SCL wear., Results: A total of 32 eyes of 29 patients (66% men) with a median age of 30.5 years were included. The common causes of CCC were Stevens-Johnson syndrome (66%) and ocular burns (16%). The most common location of symblepharon was superior (59%) with limbal involvement in most eyes (94%). Symblepharon release was combined with mucous membrane grafting (63%), amniotic membrane grafting (31%), or conjunctival autografting (6%). The median interval between symblepharon release with OSR and SCL trial was 15 weeks [interquartile range (IQR): 6-24]. The median best-corrected visual acuity improved from logMAR 1.5 (IQR: 1.2-1.8) to logMAR 1.2 (IQR: 0.6-1.4) with SCLs after symblepharon release with OSR ( P < 0.001). The median diameter of the SCL used was 15 mm (IQR: 15-16), with a median base curve of 7.9 mm (IQR: 7.9-8). Symblepharon recurrence was noted in 70% of eyes that underwent amniotic membrane grafting; no recurrence was seen with mucous membrane grafting or conjunctival autografting., Conclusions: In eyes with CCC with keratopathy and symblepharon, visual rehabilitation is possible with SCLs after symblepharon release with OSR without having to resort to a penetrating corneal procedure., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The aim of this study was to describe the indications and outcomes of flap amputation after laser in situ keratomileusis (LASIK) at a referral-based institution., Methods: In this retrospective consecutive case series, medical records of patients who underwent LASIK flap amputation at Mayo Clinic, Rochester, MN, between January 1, 1998, and January 31, 2023, were reviewed., Results: Fifteen eyes (15 patients) underwent flap amputation during the study period. The median age was 45 years (range, 25-71 years), and 8 patients (53%) were men. The median uncorrected visual acuity before flap amputation was 20/200 (range 20/40-hand motions). Indications for flap amputation included epithelial ingrowth (n = 6, 40%), infectious keratitis (n = 6, 40%), diffuse lamellar keratitis (n = 1, 7%), vegetative foreign body (n = 1, 7%), and astigmatism from fixed flap striae (n = 1, 7%). The median duration of follow-up was 8 months (range 1-234 months). Subsequent corneal interventions included chelation of calcific band keratopathy (n = 1, 7%), lamellar keratoplasty (n = 1, 7%), penetrating keratoplasty (n = 2, 18%), keratoprosthesis (n = 1, 7%), and rigid contact lens wear (n = 4, 27%). The final median best visual acuity was 20/25 (range 20/20-20/200). Compared with noninfectious indications for flap amputation, eyes with infectious indications had worse baseline median uncorrected visual acuity (hand motions vs. 20/63, P < 0.001), were more likely to undergo major corneal surgical intervention (50% vs. 11%), and had worse final median best visual acuity (20/50 vs. 20/20, P = 0.018)., Conclusions: LASIK flap amputation is sometimes necessary to control threatening corneal diseases. Excellent visual outcomes were achieved in most cases, albeit with additional intervention or rigid contact lens wear., Competing Interests: S. V. Patel is a consultant to Santen Inc, Design Therapeutics Inc, and Invirsa Inc, and is developer of V-FUCHS which Mayo Clinic licenses to commercial entities (Iris Medicine, Aerie Pharmaceuticals, Santen Inc, Trefoil Therapeutics Inc, Design Therapeutics Inc, and Kowa Research Institute). The remaining authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To provide the long-term outcome of patients with end-stage severe ocular surface disease (OSD) consecutively treated with cultivated oral mucosal epithelial transplantation (COMET) followed by limbal-rigid contact lens (CL)-wear therapy., Design: Retrospective cohort., Methods: In 23 eyes of 18 patients with severe OSD who underwent COMET surgery between 2002 and 2019 and who were followed with limbal-rigid CL-wear therapy for at least 1 year postoperative, patient demographics, best-corrected visual acuity (BCVA, logMAR), Ocular Surface Grading Scores (OSGS), surgical indication and adverse events were reviewed. Primary and secondary outcomes were BCVA and OSGS changes at baseline and final examination, respectively., Results: This study involved 16 patients with Stevens-Johnson syndrome and 2 patients with mucous membrane pemphigoid (mean age: 59±15 years). The indications for COMET were as follows: corneal reconstruction for vision improvement (10 eyes (43.5%)), corneal reconstruction for persistent epithelial defect (4 eyes (17.4%)) and conjunctival (fornix) reconstruction for symblepharon release (9 eyes (39.1%)). The mean duration of CL-wear postsurgery was 6.4±3.9 years (range: 1.4 to 13.3 years). The mean BCVA at baseline and at final follow-up was logMAR 1.9±0.5 and 1.3±0.7, respectively (p<0.05). Compared with those at baseline, the OSGSs for symblepharon and upper and lower fornix shortening showed significant improvement at each follow-up time point post treatment initiation. No serious intraoperative or postoperative adverse events were observed., Conclusion: In patients afflicted with severe OSD, COMET combined with limbal-rigid CL-wear therapy postsurgery was found effective for vision improvement and ocular surface stabilisation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To report the visual outcomes and survival analysis of keratoprosthesis without contact lens wearing in a tertiary eye care hospital in Mexico City, Asociación Para Evitar La Ceguera (APEC, Coyoacán, México)., Design: Retrospective cohort with survival analysis., Participants: Twenty-three eyes (22 patients) received KPro type 1 between 2015 and 2020 with a follow-up time of three years., Methods: We included analyzed data about past medical history, preoperative diagnosis, best-spectacle visual acuity (BSCVA), postoperative complications and retention rate. Univariate, bivariate and survival analysis were performed and reported., Results: The mean age was 58 ± 13.5 years (SD). 60.86% were male patients (14 eyes). Twelve-eyes (52%) achieved a BSCVA of 20/200 or better in the first and second year of follow-up. At 3 years, only 35% achieved 20/200 or better (BSCVA). Retention rate of Boston type 1 KPro was 87% (20 eyes) at 3 years follow-up. The most common complication was retroprosthetic membrane (RPM) which occurred in 9 eyes (39.1%), followed by corneal melting in 7 eyes (30.4%)., Conclusions: We report the results of a retrospective cohort of twenty-three eyes (22 patients) who were implanted with a Boston type 1 KPro without contact lens wearing to treat corneal blindness. BSCVA improved significantly in most patients achieving 20/200 or better at the 2-year follow-up. Retention rate was 87%, with the presence of RPM as the most common complication.

Purpose: The aim of this study was to investigate mediators of visual acuity in ultrathin Descemet stripping automated endothelial keratoplasty (UT-DSAEK) compared with Descemet membrane endothelial keratoplasty (DMEK)., Methods: This was a prespecified secondary analysis of the Descemet Endothelial Thickness Comparison Trial, a prospective, randomized controlled trial comparing UT-DSAEK with DMEK. Subjects with Fuchs endothelial dystrophy or pseudophakic bullous keratopathy presenting to 2 academic centers were enrolled and randomized to either UT-DSAEK (n = 25 eyes) or DMEK (n = 25 eyes). Higher order aberrations (HOAs) and corneal densitometry were measured with Pentacam Scheimpflug imaging at 3, 6, 12, and 24 months., Results: The posterior corneal surface at the 6.0-mm optical zone had significantly less total HOAs ( P <0.001) in the DMEK group compared with UT-DSAEK at 24 months. Anterior and posterior corneal densitometry improved from baseline to 24 months for both UT-DSAEK and DMEK, but there was no significant difference between the 2 groups. Corneal densitometry and posterior HOAs were both associated with best-corrected visual acuity ( P <0.05). DMEK had 1.3 logarithm of the minimum angle of resolution better visual acuity compared with UT-DSAEK at 24 months. Approximately 64% of this effect was mediated through posterior HOAs, whereas none was mediated through anterior HOAs or densitometry., Conclusions: Decreased posterior HOAs mediate better visual acuity and account for improved vision after DMEK compared with UT-DSAEK. Corneal light scatter as measured by densitometry is similar between UT-DSAEK and DMEK, indicating that the increased thickness and stromal-stromal interface in UT-DSAEK do not significantly affect visual acuity., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To review the literature focusing on the clinical outcomes of KeraKlear (KK) (KeraMed), a foldable intrastromal keratoprosthesis., Methods: We searched 6 databases using 4 keywords: KeraKlear, Foldable Keratoprosthesis, Intrastromal Keratoprosthesis, and Non-penetrating Keratoprosthesis. Included studies had to be conducted in vivo on humans, published until January 3, 2023, and had to investigate the implantation of the KK. Eyes were considered at high risk of keratoprosthesis retention failure whenever there was an active inflammatory ocular surface disorder or in case of previous KK failure. We aimed at recording the postoperative complications, rate of prosthesis retention, and mean improvements in visual acuity., Results: We identified 144 publications, 6 of which (38 eyes) met the inclusion criteria. No randomized controlled trials were found, and some studies had significant limitations regarding sample size and follow-up duration. With a mean follow-up of 28 ± 18.8 months, postoperative complications of any kind occurred between 0% and 50% and 24% had an implant extrusion/needed a reoperation. The mean postoperative visual acuity improvement on the last follow-up was -0.83 ± 0.27 LogMAR, that is, -0.57 ± 0.3 for high-risk and -1.03 ± 0.25 for low-risk eyes, whereas 1 year after implantation, 50% of the prostheses were retained in the former and 81% in the latter group. None of the eyes developed glaucoma, endophthalmitis, or expulsive hemorrhages; none had to be eviscerated/enucleated., Conclusions: Despite the limited quality and quantity of evidence, the available literature seems to suggest the KK to be a valuable tool in the treatment of complicated corneal disorders. Because in many parts of the world, the access to corneal transplantation is limited, this prosthesis could represent a valid alternative., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The efficacy and safety of Descemet's membrane endothelial keratoplasty (DMEK) and ultrathin Descemet stripping automated endothelial keratoplasty (UT-DSAEK) have been recently compared in several systematic reviews (SRs). The aim of this study was to assess the evidence quality of such SRs, in order to obtain a scientifically rigorous comparison between the two techniques. We performed a systematic review of SRs and meta-analyses comparing the efficacy and safety between UT-DSAEK and DMEK up to 24th March 2023, using 3 electronic databases (PubMed, Cochrane Library, Google Scholar) plus manual reference search. Specific outcomes analyzed included best-corrected visual acuity (BCVA), endothelial cell density (ECD), rebubbling rate, and other postoperative complications. Of 90 titles/abstracts screened, four SRs met the inclusion criteria. All SRs adequately analyzed potential bias of the included studies. One SR raised concern for potential literature search bias and two SRs have heterogeneity in some outcomes analyzed. All SRs found higher BCVA after DMEK, but one SR reported significant heterogeneity. All SRs found significant heterogeneity in ECD analysis, with one SR providing inconsistent analysis of this outcome. Three SRs analyzed rebubbling rates, favoring UT-DSAEK over DMEK. Three SRs concluded a higher overall complication rate after DMEK, although rebubbling may be a confounding factor. This systematic review clarifies the strengths and weaknesses of published SRs and reinforces the conclusion that DMEK leads to superior visual outcomes compared to UT-DSAEK, with the trade-off of higher rebubbling rates and possibly other postoperative complications. Studies with longer follow-up are needed to ascertain these differences between procedures., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: To investigate the clinical efficacy and safety of the modified Cretan protocol in patients with post-laser in situ keratomileusis ectasia (PLE)., Materials and Methods: In this retrospective study, 26 eyes of 16 patients with PLE were treated with the modified Cretan protocol (combined transepithelial phototherapeutic keratectomy and accelerated corneal collagen cross-linking). Visual, refractive, tomographic, and aberrometric outcomes and point spread function (PSF) were recorded preoperatively and at 6, 12, and 24 months after treatment., Results: Both uncorrected and best corrected visual acuity were stable at 24 months postoperatively compared to baseline (from 0.89±0.36 to 0.79±0.33 logarithm of the minimum angle of resolution [LogMAR] and 0.31±0.25 to 0.24±0.19 LogMAR, respectively, p>0.05 for all values). The mean K1, K2, Kmean, thinnest corneal thickness, and spherical aberration at baseline were 45.76±5.75 diopters (D), 48.62±6.17 D, 47.13±5.89 D, 433.16±56.86 μm, and -0.21±0.63 μm respectively. These values were reduced to 42.86±6.34 D, 45.92±6.74 D, 44.21±6.4 D, 391.07±54.76 μm, and -0.51±0.58 μm at 24 months postoperatively (p<0.001, p=0.002, p<0.001, p=0.001, and p=0.02, respectively). The mean spherical equivalent, manifest cylinder, Kmax, central corneal thickness, other corneal aberrations (root mean square, trefoil, coma, quatrefoil, astigmatism), and PSF remained stable (p>0.05 for all variables), while anterior and posterior elevation were significantly improved at 24 months postoperatively (p<0.001 and p=0.02, respectively). No surgical complications occurred during the 24-month follow-up., Conclusion: The modified Cretan protocol is a safe and effective treatment option for PLE patients that provides visual stabilization and significant improvement in topographic parameters during the 24-month follow-up. Further studies are needed to support our results., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (©Copyright 2024 by the Turkish Ophthalmological Association / Turkish Journal of Ophthalmology published by Galenos Publishing House.)

Purpose: To summarize the outcomes of corneal sight rehabilitating surgery in Stevens-Johnson syndrome (SJS)., Methods: This is a retrospective analysis of a consecutive case series. Twenty-four eyes of 18 SJS patients were included in this study. The ocular parameters, surgical procedures, postoperative complications, and additional treatments of the cases were reviewed., Results: A total of 29 corneal sight rehabilitating surgeries, which consists of 9 keratoplasties, 8 Keratolimbal allograft (KLAL) and 12 combined surgeries (keratoplasty and KLAL simultaneously) were performed on the 24 eyes. All patients were treated with glucocorticoid eyedrops and tacrolimus eyedrops for anti-rejection treatment without combining systemic immunosuppression, except two patients who were prescribed prednisone tablets for the management of systemic conditions. The mean follow-up period was 50.6 ± 28.1 months. The optimal visual acuity (VA) (0.74 ± 0.60 logarithm of the minimum angle of resolution [logMAR]) and endpoint VA (1.06 ± 0.82 logMAR) were both significantly better than the preoperative VA (1.96 ± 0.43 logMAR) (95% CI, p = 0.000). 57.1% patients (8/14) were no longer in the low vision spectrum, and 88.9% patients (8/9) were no longer blind. The mean epithelialization time was 7.1 ± 7.6 weeks. The success rate was 86.7%. Additional treatments for improving epithelialization included administration of serum eyedrops (n = 10), contact lens (n = 15), amniotic membrane transplantation (n = 6), and tarsorrhaphy (n = 8). Complications included delayed epithelialization (n = 4, over 12 weeks), glaucoma (n = 11), and severe allograft opacity (n = 4). Only one graft rejection was observed., Conclusions: Keratoplasty and KLAL can remarkably enhance VA and improve low vision or even eliminate blindness for ocular complications of SJS. The outcome of the surgeries was correlated with the preoperative ocular situation and choice of operative methods., (© 2024. The Author(s).)

Objective: Evaluation of clinical efficacy and safety of tobramycin/dexamethasone eye ointment in treating persistent corneal epithelial dysfunction (PED) after cataract surgery., Methods: 26 cases diagnosed as PED after cataract surgery accept the tobramycin/dexamethasone ophthalmic ointment and intense pulse light treatment in the Xiamen University of Xiamen eye center between September 2016 and April 2022 were retrospectively analyzed, mainly including clinical manifestations, characteristics of morphological changes imaged by in vivo confocal microscopy, meibomian glands infrared photography, lipid layer thickness (LLT), management and therapeutic effects., Results: There were 26 eyes, include 8(35%) males and 15(65%) females with an average age of 69.6 ± 5.2 years(50 to 78 years). The mean hospitalization time was (18.4 ± 7.5) days after cataract surgery. Twenty patients had meibomian gland dysfunction. Infrared photography revealed varying loss in the meibomian glands, with a mean score of 3.8 ± 1.2 for gland loss. The mean LLT was 61.6 ± 8.4 nm. After treatment, 20 patients were cured, and 3 received amniotic membrane transplantation. After treatment, the uncorrected visual acuity (UCVA) and best-corrected vision activity (BCVA) improved (P < 0.001), and there was no significant difference in intraocular pressure (IOP) before and after treatment (P > 0.05)., Conclusions: The early manifestation of PED after surgery is punctate staining of the corneal epithelium. Tobramycin and dexamethasone eye ointment bandages have a good repair effect. The meibomian gland massage combined with intense pulse light treatment can effectively shorten the course of the disease., (© 2024. The Author(s).)

Acquired corneal diseases such as dry eye disease (DED), keratitis and corneal alkali burns are significant contributors to vision impairment worldwide, and more effective and innovative therapies are urgently needed. The Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) signaling pathway plays an indispensable role in cell metabolism, inflammation and the immune response. Studies have shown that regulators of this pathway are extensively expressed in the cornea, inducing significant activation of JAK/STAT3 signaling in specific acquired corneal diseases. The activation of JAK/STAT3 signaling contributes to various pathophysiological processes in the cornea, including inflammation, neovascularization, fibrosis, and wound healing. In the context of DED, the hypertonic environment activates JAK/STAT3 signaling to stimulate corneal inflammation. Inflammation and injury progression in infectious keratitis can also be modulated by JAK/STAT3 signaling. Furthermore, JAK/STAT3 signaling is involved in every stage of corneal repair after alkali burns, including acute inflammation, angiogenesis and fibrosis. Treatments modulating JAK/STAT3 signaling have shown promising results in attenuating corneal damage, indicating its potential as a novel therapeutic target. Thus, this review emphasizes the multiple roles of the JAK/STAT3 signaling pathway in common acquired corneal disorders and summarizes the current achievements of JAK/STAT3-targeting therapy to provide new insights into future applications., Competing Interests: Declaration of competing interest No conflicts of interest, financial or otherwise, are declared by the authors., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: The aim of this study is to describe techniques, results, and open issues of corneal neurotization (CN) for the treatment of neurotrophic keratopathy (NK)., Methods: An overview of the most important studies of CN is provided. The 2 main surgical approaches (namely, direct CN and indirect CN) with specific advantages and disadvantages are described. The results regarding changes of corneal sensitivity and clarity, visual acuity, and in vivo confocal microscopy metrics are summarized. Ex vivo studies with histopathology of the neurotized cornea are reported. Intraoperative and early and late postoperative complications are described along with current open issues to be further clarified., Results: Corneal sensitivity improves after both direct and indirect CN. Corneal reinnervation allows the healing of NK in almost the totality of the operated eyes, determining a corresponding improvement of corneal clarity and visual acuity. Regeneration of corneal nerve fibers is confirmed by means of either in vivo confocal microscopy or ex vivo histopathology. Few self-limiting complications are reported during the postoperative course. Current open issues concern the identification of the technique of choice, the use of autograft or allograft, and the timing of CN either when performed alone or when combined with other surgeries., Conclusions: CN represents a game-changing surgical procedure for NK, which has the potential to restore corneal sensitivity in all stages of the disease regardless of the mechanism of denervation. Further long-term results are needed to confirm its efficacy over time. The design of randomized clinical trials comparing CN with noninterventional therapies could further validate the adoption of this technique., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The purpose of the study was to establish a simple ex vivo corneal re-epithelization model and study the labial mucosal epithelium grafting as a potential approach for ocular surface reconstruction. Four human donor corneal buttons were overstored in a corneal cold storage solution at 4 °C for 32-52 days. Four labial oral mucosa strips were dissected from four patients during fornix reconstruction after they signed informed consent. The substantia propria was trimmed off, and the resulting graft was sutured near the corneal limbus with running sutures (thus forming the tissue construct). Constructs were cultured under the standard conditions with the anterior corneal side outwards. After 3 weeks of culture, constructs were removed, washed, and fixed. Sections were stained with hematoxylin and eosin (HE), anti-keratins 4, 13, 19, and p63. Nuclei were counterstained with Hoechst. After the cultivation, all constructs were integral with the attached graft and non-loosened sutures. The native cells were absent in all donor corneas. Histological evaluation demonstrated that the labial mucosal grafts were attached to the Bowman's membrane (BM), and its cellular outgrowths were found to be transit from the graft to the BM over the anterior surface in all constructs. Cells expressed mucosal epithelial keratins 4, 13, and 19, and several were p63-positive in nuclei. In the study, a simple ex vivo corneal re-epithelization model was successfully established. The model was potent in studying the labial mucosal epithelium grafting as an option for autologous ocular surface reconstruction in patients with bilateral limbal stem cell deficiency., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: The aim of this study was to characterize the outcomes of eyes with neurotrophic keratitis (NK) treated with a course of cenegermin-bkbj in the presence of a bandage contact lens (BCL)., Methods: A retrospective chart review of all eyes with a clinical diagnosis of NK treated with cenegermin-bkbj was performed between 2018 and 2020. Inclusion criteria included cenegermin-bkbj treatment with a BCL in place. Demographics, etiology, visual acuity, pretreatment and posttreatment corneal sensation, and treatment outcomes were assessed., Results: There were 18 eyes of 16 patients (69% female) with NK treated with cenegermin-bkbj while having a BCL in place. After cenegermin-bkbj treatment, presence of corneal sensation significantly increased from 7% of eyes to 79% of eyes (P < 0.0001). There was also a significant increase in the number of quadrants with corneal sensation (mean of 0.1 quadrants increased to 1.6 quadrants, P =0.0005). Six of 10 eyes (67%; P = 0.004) with a persistent epithelial defect (PED) experienced complete resolution at the conclusion of treatment, while 3 additional eyes experienced a decrease in the defect size. Despite all 18 eyes necessitating a chronic BCL before cenegermin-bkbj treatment, 4 were able to maintain their epithelium without a BCL after treatment for at least some period., Conclusions: Cenegermin-bkbj treatment for NK with a BCL in place demonstrated improvement in corneal sensation, epithelial defect size, and fluorescein staining. In eyes demonstrating previous ocular surface decompensation with discontinuation of a BCL, maintenance of BCL use during treatment with cenegermin-bkbj may be considered., Competing Interests: There were no relevant financial conflicts of interest regarding this work. A. Y. Cheung has consulted for Alcon and LayerBio. M. L. Nordlund has consulted for Bausch and Lomb and Shire. E. J. Holland has consulted for Alcon Laboratories, Allergan, Bausch & Lomb, Kala Pharmaceuticals, Mati Pharmaceuticals, and Senju Pharmaceuticals. A. P. Shah, M. R. Denny, and K. L. Pierson do not have any disclosures to report. There was no funding received for this study., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To report the findings of a comprehensive eye examination from an individual with congenital insensitivity to pain because of loss-of-function mutations in the SCN9A gene., Methods: Ophthalmologic examination and confocal microscopy were performed on a patient with congenital insensitivity to pain., Results: A 39-year-old man with compound heterozygous mutations in the SCN9A gene underwent examination. Cochet-Bonnet esthesiometry readings averaged 38 mm (SD 8 mm) in the right eye and 55 mm (SD 7 mm) in the left eye. Other corneal findings included mild conjunctival lissamine green staining, nonvisually significant corneal scars, mild anterior basement membrane dystrophy, and a tear breakup time of 3 seconds in each eye. In vivo confocal microscopy of the corneal subbasal nerve plexus revealed relatively normal corneal nerve morphology, but a reduction in corneal nerve fiber density., Conclusions: An individual with loss-of-function mutations in SCN9A had reduced corneal nerve fiber density but normal corneal mechanoreception., Competing Interests: A. Delwig is an employee of SiteOne Therapeutics. S. G. Waxman is a consultant to SiteOne. The other authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The aim of this study was to assess clinical outcomes of corneal neurotization (CN) and determine patient perception of postoperative results., Methods: This was a retrospective study involving 29 eyes in 28 patients who underwent CN. Chart review data included demographic and clinical history; ophthalmic examination including visual acuity, ocular surface quality, and corneal sensation; surgical technique; and postoperative course. Subjective self-reported patient outcomes of surgical success were also assessed. Only eyes with at least 6 months of follow-up were included in the statistical analysis., Results: A total of 24 eyes and 23 patients were included in statistical analyses. The median postoperative follow-up time was 12.2 months (interquartile range 10.9-18.5 mo). Twenty-three eyes (92%) achieved improvement in ocular surface quality. Eleven of 13 (85%) demonstrated healing of persistent epithelial defects at their last follow-up. Patients gained a median of 2.3 cm in Cochet-Bonnet esthesiometry measurements of sensation. No significant difference was found between preoperative and postoperative visual acuity. All 17 patients who provided self-assessment of their surgical outcome indicated they would undergo CN again if given the choice. Most of the patients reported that the postoperative pain was tolerable, with a median pain score of 3.0 on a 10-point scale (interquartile range 0.0-4.0). Sixteen patients (94%) reported full or partial return of skin sensation along the donor nerve distribution., Conclusions: CN provides improvement in corneal health and sensibility, with high patient satisfaction and minimal postoperative pain and morbidity., Competing Interests: I. M. Leyngold is a consultant for AxoGen Inc. The remaining authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To characterize vision-related quality of life after penetrating keratoplasty (PKP), deep anterior lamellar keratoplasty (DALK), Descemet stripping automated endothelial keratoplasty (DSAEK), and Descemet membrane endothelial keratoplasty (DMEK) using the National Eye Institute Visual Function Questionnaire (NEI-VFQ 9)., Methods: Using the Sight Outcomes Research Collaborative ophthalmology electronic health record repository, questionnaire responses were obtained from 103 PKP patients, 24 DALK patients, 42 DSAEK patients, and 50 DMEK patients undergoing postoperative examination. No exclusions were made based on preoperative diagnosis, age, complications, or comorbidities. Associations between clinical characteristics and vision-related quality of life were analyzed using nonparametric and linear regression methods., Results: Patients were surveyed an average of 1.5 years postoperatively (range 24 d to 4.4 yrs). Participants who had undergone DALK, DMEK, DSAEK, and PKP had median composite VFQ scores of 77.8, 84.2, 76.1, and 70.6, respectively (P= 0.002). There were no significant differences in VFQ scores between patients treated with DMEK versus DSAEK (P = 0.440) or between patients treated with PKP versus DALK (P = 1.000). Higher postoperative acuities in the operative and fellow eyes were associated with higher VFQ scores (P < 0.001 and P < 0.001). When controlling for postoperative acuity by regression modeling, surgery type was not associated with patient-reported composite VFQ scores., Conclusions: In this study, patient-reported vision-related quality of life was similar among DMEK and DSAEK participants and also among DALK and PKP participants. When controlling for postoperative acuity, vision-related quality of life was similar among all study participants, irrespective of the keratoplasty technique., Competing Interests: G. E. Dunbar reported receiving a grant from Eversight. M. A. Woodward reported receiving grants from National Institutes of Health (NIH-1R01EY031033) and the Michigan Institute for Clinical & Health Research (MICHR). The remaining authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Aims: To evaluate the contrast sensitivity in patients with nuclear cataract and corneal guttae compared to patients with nuclear cataract without guttae., Methods: In this retrospective, single-centre case series, 50 eyes of 50 patients fulfilling the inclusion criteria were enrolled. Patients with corneal guttae and nuclear cataract (n=25, study group) underwent triple Descemet membrane endothelial keratoplasty (DMEK). Patients with nuclear cataract and healthy corneas underwent cataract surgery (n=25, control group). Inclusion criteria were preoperative best-corrected visual acuity ≥20/40, no corneal oedema and similar lens opacity (nuclear opalescence 2.0-2.9). Outcome measures included MARS letter and OPTEC 6500P contrast sensitivity test, corneal volume, central corneal thickness and anterior and posterior corneal densitometry., Results: Preoperative MARS letter and OPTEC 6500P contrast sensitivity was significantly worse in the study group (MARS: p<0.001; OPTEC 6500P: p<0.007 at low spatial frequencies in daylight with and without glare and nightlight without glare). After surgery, there was no significant difference in MARS letter contrast sensitivity between groups (p=0.225). OPTEC 6500P contrast sensitivity remained significantly lower in the study group in daylight and nightlight with and without glare at most spatial frequencies (p<0.01) postoperatively. Preoperative and postoperative corneal volume, central corneal thickness and anterior corneal densitometry were equal in both groups (p>0.05). Posterior densitometry was significantly higher in the study group than in the control group preoperatively (p<0.001) but turned into equal values postoperatively (p=0.07)., Conclusions: Corneal guttae cause an additional significant decrease in contrast sensitivity in eyes with nuclear cataract. This is in favour of performing a triple DMEK even in eyes with a visual acuity of ≥20/40., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To compare 4-year survival outcomes of Descemet membrane endothelial keratoplasty (DMEK) and Descemet-stripping automated endothelial keratoplasty (DSAEK) in eyes with previous glaucoma surgery., Methods: This is a retrospective, comparative case series, including patients with previous trabeculectomy or glaucoma drainage device implantation, who later underwent either DMEK (n = 48) or DSAEK (n = 41). Follow-up was limited to 12 to 60 months to prevent bias. Primary outcomes were graft survival and rejection. Secondary outcomes were best spectacle-corrected visual acuity (BSCVA), detachment/rebubble, endothelial cell loss, and intraocular pressure elevations., Results: Baseline characteristics, follow-up duration, and preexisting glaucoma parameters did not differ significantly between the groups. Graft survival probability after DMEK and DSAEK was 75% and 75% at 1 year, 63% and 50% at 2 years, 49% and 44% at 3 years, 28% and 33% at 4 years, and 28% and 29% at 5 years, respectively (P = 0.899 between the groups). Graft rejection rates were 20.8% and 19.5%, respectively (P = 1.000). Primary failure, rebubbling, endothelial cell loss, and intraocular pressure elevation did not differ significantly between the groups. Preoperative BSCVA did not differ between the groups (P = 0.821). Postoperative BSCVA was significantly better in the DMEK group at 6, 12, and 24 months (P < 0.001, P = 0.022, and P = 0.047, respectively). In a multivariable model (R2 = 0.576), the type of surgery was the only significant factor affecting postoperative BSCVA, in favor of DMEK (coefficient value -0.518, P = 0.002)., Conclusions: In eyes with previous glaucoma surgery, DMEK and DSAEK had comparably low survival and comparably high rejection rates. Postoperative visual acuity might be better after DMEK in this setting., Competing Interests: D. S. Rootman: consultant for Alcon; received research funding from Johnson & Johnson. C. C. Chan: consultant for Shire and Allergan; received honoraria from Santen, Shire, Johnson & Johnson, Allergan, Alcon, Bausch & Lomb, Zeiss and Labtician Thea; received research funding from Shire, Allergan, Bausch & Lomb and Tear Laboratory. A. R. Slomovic: consultant for Alcon, Bausch & Lomb, Santen and Abbvie; advisory board member at Allergan and Shire; received research funding from AMO. M. Mimouni: consultant for Eye Yon Medical and Lapidot Medical. The remaining authors have no conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

A properly functioning cornea is critical to clear vision and healthy eyes. As the most anterior portion of the eye, it plays an essential role in refracting light onto the retina and as an anatomical barrier to the environment. Proper vision requires that all layers be properly formed and fully intact. In this article, we discuss the role of the epidermal growth factor receptor (EGFR) in maintaining and restoring the outermost layer of the cornea, the epithelium. It has been known for some time that the addition of epidermal growth factor (EGF) promotes the restoration of the corneal epithelium and patients using EGFR inhibitors as anti-cancer therapies are at increased risk of corneal erosions. However, the use of EGF in the clinic has been limited by downregulation of the receptor. More recent advances in EGFR signaling and trafficking in corneal epithelial cells have provided new insights in how to overcome receptor desensitization. We examine new strategies for overcoming the limitations of high ligand and receptor expression that alter trafficking of the ligand:receptor complex to sustain receptor signaling.

Purpose: To evaluate the surgical and 3-year clinical outcomes of modified big-bubble 9-mm deep anterior lamellar keratoplasty (DALK) in eyes with previous ALK (ALK)., Methods: In this interventional case series, 21 consecutive eyes with unsatisfactory vision after ALK (superficial ALK n = 9; laser-assisted ALK n = 7; and epikeratophakia n = 5) underwent large-diameter (9-mm) DALK. The surgery involved deep trephination based on the anterior segment optical coherence tomography pachymetry measurement at 9-mm diameter, pneumatic dissection from the base of the trephination and limited stromal clearance of the optical zone (6 mm). Main outcome measures were success rates of pneumatic dissection, best spectacle-corrected visual acuity, and complication rates., Results: Pneumatic dissection with type 1 bubble formation succeeded in 19 (90%) eyes. In the 2 remaining cases, the 6-mm optical zone was cleared by manual dissection. Perforation occurred in one of the latter cases; no procedure was converted to penetrating keratoplasty. One month after complete suture removal, the preoperative mean best spectacle-corrected visual acuity (0.75 ± 0.23 logMAR) improved to 0.09 ± 0.10 logMAR (P < 0.001) and remained stable up to 3 years after surgery. At the final follow-up, refractive astigmatism was ≤4.5 and <6 D in 20 (95%) and 21 (100%) eyes, respectively. Stromal rejection was observed in 2 eyes (10%) and was treated successfully with steroids., Conclusions: Even in eyes with previous ALK, pneumatic dissection can be achieved through a modified DALK technique with a low risk of complications and excellent visual and refractive outcomes., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To study the change in contrast sensitivities in eyes with Fuchs endothelial dystrophy and bullous keratopathy after Descemet membrane endothelial keratoplasty (DMEK)., Methods: In this prospective study, 50 pseudophakic eyes of 50 patients who received DMEK surgery at the Charité-Universitätsmedizin Berlin were included. Visual acuity; contrast sensitivity using OPTEC 6500 at spatial frequencies of 1.5, 3, 6, 12, and 18 cycles/degree in photopic and mesopic light with and without glare; central corneal thickness (CCT); and anterior and posterior corneal aberrations were measured preoperatively and at 3 and 12 months postoperatively., Results: Best-corrected visual acuity (preoperative 0.67 ± 0.46 and after 12 months 0.19 ± 0.16 LogMAR, P < 0.001) and photopic and mesopic contrast sensitivities with and without glare improved significantly, whereas CCT decreased significantly (preoperative 677 ± 114 μm, after 12 months 527 ± 29 μm, P < 0.001). Preoperative CCT correlates significantly with preoperative photopic contrast sensitivity (correlation coefficient -0.462, P = 0.002), and postoperative total anterior aberrations correlates with postoperative photopic contrast sensitivity (correlation coefficient -0.361, P = 0.006)., Conclusions: Photopic and mesopic contrast sensitivities, especially with glare, are impaired in patients with Fuchs endothelial dystrophy and bullous keratopathy. The extent of the corneal thickening seems to mainly influence the contrast sensitivity preoperatively. DMEK surgery improves the contrast sensitivity significantly. However, higher postoperative anterior corneal aberrations limit the postoperative contrast sensitivities., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Posterior lamellar keratoplasty is increasingly applied in patients with endothelial decompensation after penetrating keratoplasty (PK). The aim of this study was to compare the results of Descemet membrane endothelial keratoplasty (DMEK) and Descemet stripping automated endothelial keratoplasty (DSAEK) after PK., Methods: In this retrospective study, clinical data of 30 patients who received DMEK (n = 19) or DSAEK (n = 11) for endothelial decompensation after PK were evaluated. All lamellar keratoplasties were performed at the Department of Ophthalmology at University Hospital Mainz, Germany. Primary end point included best-corrected visual acuity, and secondary end points included endothelial cell density, rebubbling, and rejection rates, all at 6 and 12 months., Results: After 6 months and 12 months, 89% of DMEK and 73% of DSAEK grafts and 63% of DMEK and 64% of DSAEK grafts provided sufficient corneal deturgescence, respectively, represented by improvement in best-corrected visual acuity. DMEK group median preoperative Logarithm of the Minimum Angle of Resolution visual acuity of 1 increased to 0.5 after 6 and 12 months. DSAEK group median Logarithm of the Minimum Angle of Resolution visual acuity increased from 3 to 2 and 1.3 after 6 and 12 months. After 12 months, graft endothelial cell density had decreased by 58% in the DMEK group and by 59% in the DSAEK group. The proportion of patients requiring a rebubbling were 63% in the DMEK and 64% in the DSAEK group. No lamellar graft rejection occurred in either trial arm., Conclusions: Both DMEK and DSAEK significantly improved visual acuity in patients after PK. Lamellar graft survival, loss of endothelial cells, and mean rebubbling rates were similar in both groups., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To evaluate the efficacy of autologous blood eye drops in patients diagnosed with severe ocular surface disease and dry eye who were unresponsive to conventional therapy and who would otherwise be considered for autologous serum eye drops., Methods: A total of 38 eyes of 19 patients (15 women and 4 men) with ocular surface disease and severe dry eye refractory to conventional treatment were treated with fingerprick autologous blood 4 times daily for 6 months. Follow-up visits occurred at 1-, 3-, and 6-month intervals. At each visit, visual acuity, Oxford Grading Scheme score, tear film break-up time, Schirmer test, and ocular surface disease index were measured., Results: There was a significant improvement in the ocular surface staining score at all time gates. The mean score at presentation was 2.13, and this improved to 1.50 at 1 month (P < 0.001), 1.29 at 3 months (P < 0.01), and 1.42 at 6 months (P < 0.01). There was an improvement in tear film break-up time from 4.75 seconds at baseline to 6.79 seconds at 3 months (P < 0.01) and 7.0 seconds at 6 months (P < 0.001). An improvement in the Schirmer test was only found at 6 months with an improvement from 3.67 mm to 13.33 mm (P < 0.05). There was no statistical change in visual acuity at any time gate or ocular surface disease index score, although 83% of patients reported an improvement in their symptoms at 6 months. There were no adverse events reported., Conclusions: Fingerprick autologous blood is an effective, readily accessible, and safe therapy for the treatment of recalcitrant cases of severe ocular surface disease and dry eye unresponsive to conventional therapy., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Corneal involvement in HIV-infected individuals may be broadly classified into two categories, namely, infectious and noninfectious with the vast majority of manifestations occurring in the former. In this article, we shall focus on these two categories and strive to highlight those presentations that should alert the clinician to suspect underlying HIV infection. Infectious group mainly consists of Herpitic group of viral infections. Bacterial causes may be due to Staphylococcus epidermidis, Staphylococcus aureus, Pseudomonas aeroginosa , alpha hemolytic Streptococcus, Micrococcus and Bacillus . Fungalf keratitis in HIV-infected individuals depends on the geographic locations from which patient comes. Microsporidia and Acanthamoeba are common Protozoal causes. Non-infective inflammatory causes include peripheral ulcerative keratitis, keratoconjunctivitis sicca, and squamous cell carcinoma of the conjunctiva. Severity which is abnormally severe or very minimally reactive makes the clinician suspect of immunosuppression.

Background: To evaluate the anatomical and functional outcomes of autologous contralateral penetrating keratoplasty (autokeratoplasty)., Methods: Kaplan-Meier survival analyses were retrospectively performed. Anatomical failure was defined as regraft or graft permanently cloudy at any time during follow-up. Functional failure was defined as the final best-corrected visual acuity (BCVA) <20/400., Results: Thirty-one eyes of 31 patients (19 men), with a mean age of 52±18 years (range 15-81 years) were studied during a mean follow-up of 11.3 years (from 13 months to 48 years). At 12 months postoperatively, all the recipient eyes showed a transparent cornea, but 23% showed functional failure. At the final followup, 16 recipient eyes (52%) showed anatomical and functional success. Twenty-three eyes (74%) showed a clear cornea and 68% reached a better BCVA when compared with preoperative measurements. Nevertheless, 13/31 eyes (42%) displayed functional failure. The accumulative probabilities for anatomical success were 100%, 72% and 48% and 77%, 59% and 29% for functional success at 1, 10 and 40 years, respectively. The most common risk factor for failure was progression of previous glaucoma in 50% of the anatomical failures and in 77% of the functional failures., Conclusions: Autokeratoplasty could be a successful long-term option in patients having one eye with a clear cornea but with irreversible visual dysfunction and the contralateral eye having favourable visual potential limited only by a completely opacified cornea. Progression of previous glaucoma was the most important risk factor for long-term cornea decompensation and visual functional failure in the sample., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To evaluate changes in the anterior chamber of eyes that have undergone Descemet membrane endothelial keratoplasty (DMEK) and to identify factors that affect these changes., Methods: This retrospective study included 25 pseudophakic eyes of 25 patients who underwent DMEK. We determined the preoperative and postoperative values of the best spectacle-corrected visual acuity, spherical equivalent (SE), anterior chamber volume (ACV), anterior chamber depth (ACD), central corneal thickness (CCT), and scleral spur angle (SSA) evaluated using anterior segment optical coherence tomography and iris damage score and iris posterior synechiae score. We defined ∆ as the average change rate from the preoperative to postoperative value for each factor at 1 month (SE at 6-12 months) postoperatively. We also analyzed correlations between ∆ACV, ∆SE, and other preexisting factors., Results: Compared with the preoperative ACV value (128 ± 28 mm3), the postoperative value significantly increased to 155 ± 21 mm3 (P < 0.001); ∆SE was +1.01 ± 1.09 diopters. ∆ACV was negatively correlated with preoperative ACD (R = 0.643, P < 0.001) and SSA (R = 0.555, P = 0.001) and positively correlated with ∆ACD (R = 0.799, P < 0.001) and ∆SSA (R = 0.608, P < 0.001). ∆CCT, iris damage score, and iris posterior synechiae score were not significantly correlated with ∆ACV. ∆SE was positively correlated with ∆ACV, ∆ACD, and ∆SSA (R = 0.680, 0.455, and 0.478; P < 0.001, <0.05, and <0.05, respectively)., Conclusions: An increase in the ACV and hyperopic change was noted after successful DMEK, especially in eyes with narrow-angled shallow anterior chambers., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: To develop a nomogram to predict the 3- and 5-year likelihood of graft survival after penetrating keratoplasty (PK) based on preoperative assessment and intraoperative plan., Design: Retrospective clinical case-control study., Methods: Data from 1,029 consecutive PKs in 903 eyes of 835 patients performed at a single tertiary center from May 2007 to September 2018 were extracted from electronic medical records and evaluated for corneal graft failure, defined as irreversible and visually significant graft edema, haze, or scarring. Thirty-seven variables were assessed by multivariable Cox models. A nomogram to predict the probability of graft survival was created., Results: Mean recipient age was 57.1 ± 22.0 years and mean follow-up was 4.22 ± 3.05 years. Overall, 37.4% of grafts failed during follow-up. Eleven variables were significantly associated with graft failure, including active microbial infection at the time of PK (hazard ratio [HR] = 5.10, 95% confidence interval [CI] 3.53-7.37), intraocular silicone oil at the conclusion of the PK (HR = 4.28, 95% CI 2.38-7.71), history of systemic autoimmune disease (HR = 2.83, 95% CI 1.63-4.90), 4 quadrants of corneal neovascularization (HR = 2.76, 95% CI 1.56-4.86), any prior anterior segment surgery (HR = 2.41, 95% CI 1.55-3.75), and lens status as anterior chamber intraocular lens at the conclusion of surgery (HR = 2.35, 95% CI 1.30-4.26). The nomogram exhibited a concordance index of 0.76 (95% CI 0.74-0.78); internal calibration plots depicted strong correlation between prediction and observation of graft survival., Conclusions: PK graft prognosis may be predicted relatively accurately based on 11 variables. Although established from retrospective data, this nomogram would be valuable for data-driven patient counseling prior to corneal transplantation., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To report the outcomes after Descemet membrane endothelial keratoplasty (DMEK) in vascularized eyes., Methods: Consecutive cases of DMEK in vascularized eyes (involving ≥2 vascularized quadrants) were selected from a prospective database. Best corrected visual acuity, endothelial cell density (ECD), central corneal thickness, corneal transplant rejection episode, graft survival, and area of neovascularization (quantified using image analysis software) were evaluated., Results: In this study, 24 eyes of 24 patients were selected [mean age, 65.0 years; mean follow-up duration, 14.8 months (6-36 months)], which consists of 14 vascularized eyes after failed penetrating keratoplasty and 10 vascularized eyes with bullous keratopathy. Best corrected visual acuity improved from 1.60 ± 1.02 LogMAR preoperatively to 0.47 ± 0.37 LogMAR 12 months postoperatively (P < 0.001). Central corneal thickness decreased from 824 ± 193 μm preoperatively to 544 ± 48 μm 12 months postoperatively (P = 0.001). The donor ECD decreased from 2272 ± 723 cells/mm2 preoperatively to 1570 ± 279 cells/mm2 12 months postoperatively. The total loss of ECD at the last visit was 40.7% ± 13.0%. Eight of 24 eyes (33.3%) required rebubbling, which resulted in final attachment. The corneal neovascularization area significantly regressed from 4.68% ± 3.26% preoperatively to 2.28% ± 1.58% (n = 18, P = 0.021). Corneal transplant rejection episodes occurred in 1 eye of 24 patients (4.2%). There was no primary graft failure., Conclusions: DMEK is a feasible option to treat endothelial dysfunction in vascularized eyes., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To evaluate glaucoma risk factors and associated outcomes of the Boston keratoprosthesis type I (KPro)., Design: Clinical case-control study., Methods: This is a single-center study of 140 eyes of 118 patients who underwent KPro surgery between October 2008 and March 2017 by a single surgeon. A total of 118 eyes of 118 patients with at least 6 months of follow-up were analyzed to account for intereye correlation. Patients without glaucoma were compared to those diagnosed with glaucoma, which included treatment with intraocular pressure (IOP)-lowering medications or glaucoma surgery. A subgroup analysis compared eyes with pre-KPro glaucoma with those with post-KPro glaucoma. Statistical analysis was performed using univariate and multivariate analyses and Kaplan-Meier survival curves. Main outcome measures were glaucoma diagnosis and progression. Other outcomes included demographics, preoperative diagnosis, best-corrected visual acuity, IOP, cup-to-disc ratio progression and postoperative complications., Results: The mean age at surgery was 60.7 ± 16.7 years, with a follow-up of 6.9 ± 3.2 years. De novo KPro glaucoma incidence was 24% (n = 28/118), equivalent to 3.4 cases per 100 eye-years, with onset at 2.1 ± 2.2 postoperative years. A total of 17 of 118 eyes (14%) did not have glaucoma. Multiple logistic regression showed that high preoperative IOP was a predictor of higher rates of glaucoma development (odds ratio [OR] = 1.538, 95% confidence interval [CI] = 1.030-2.297, P = .035) and progression (OR = 1.450, 95% CI = 1.084-1.937, P = .012). Stromal and endothelial disorders were protective preoperative diagnoses for glaucoma progression after KPro (OR = 0.002, 95% CI = 0.000-0.227, P = .010). A greater proportion of eyes with autoimmune and ocular surface diseases developed de novo glaucoma after KPro compared with other preoperative diagnoses (P < .05). A total of 45% of glaucomatous KPro eyes suffered postoperative glaucoma progression. The mean final best-corrected visual acuity of the cohort was 1.76 ± 1.0, with no difference between eyes with and without glaucoma (P > .05). The rate of serious vision-threatening complications was higher in KPro eyes without glaucoma (77%) than in those with glaucoma (41%, P = .006)., Conclusions: High preoperative IOP signals a higher risk for glaucoma development and progression after KPro surgery. Autoimmune diseases and ocular surface diseases precipitate de novo glaucoma, whereas stromal and endothelial disorders protect against glaucoma progression after KPro. The minority of KPro eyes without glaucoma remain at high risk of complications that can hinder promising visual outcomes. Despite all available treatments and surgical interventions, a majority of eyes will suffer from glaucoma progression, even later during follow-up., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: The cornea is richly innervated by the trigeminal ganglion (TG) and its function supported by secretions from the adjacent lacrimal (LG) and meibomian glands (MG). In this study we examined how pigment epithelium-derived factor (PEDF) gene deletion affects the cornea structure and function., Methods: We used PEDF hemizygous and homozygous knockout mice to study effects of PEDF deficiency on corneal innervation assessed by beta tubulin staining, mRNA expression of trophic factors, and PEDF receptors by adjacent supporting glands, corneal sensitivity measured using a Cochet-Bonnet esthesiometer, and tear production using phenol red cotton thread wetting., Results: Loss of PEDF was accompanied by reduced corneal innervation and sensitivity, increased corneal surface injury and tear production, thinning of the corneal stroma and loss of stromal cells. PEDF mRNA was expressed in the cornea and its supporting tissues, the TG, LG, and MG. Deletion of one or both PEDF alleles resulted in decreased expression of essential trophic support in the TG, LG, and MG including nerve growth factor, brain-derived neurotrophic growth factor, and GDNF with significantly increased levels of NT-3 in the LG and decreased EGF expression in the cornea. Decreased transcription of the putative PEDF receptors, adipose triglyceride lipase, lipoprotein receptor-related protein 6, laminin receptor, PLXDC1, and PLXDC2 was also evident in the TG, LG and MG with the first three showing increased levels in corneas of the Pedf+/- and Pedf-/- mice compared to wildtype controls. Constitutive inactivation of ERK1/2 and Akt was pronounced in the TG and cornea, although their protein levels were dramatically increased in Pedf-/- mice., Conclusions: This study highlights an essential role for PEDF in corneal structure and function and confirms the reported rescue of exogenous PEDF treatment in corneal pathologies. The pleiotropic effects of PEDF deletion on multiple trophic factors, receptors and signaling molecules are strong indications that PEDF is a key coordinator of molecular mechanisms that maintain corneal function and could be exploited in therapeutic options for several ocular surface diseases.