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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.)

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: 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.)

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: 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 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.)

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.)

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.)

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 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.

Purpose: To investigate the possibility of detecting presumed corneal blood staining after traumatic hyphema with corneal densitometry and to evaluate corneal transparency after hyphema resolution., Methods: Twenty-eight patients with uniocular nonpenetrating ocular trauma with hyphema were included in the study. Corneal densitometry measurements were performed at the first week and the first month after full resolution of blood in the anterior chamber and discontinuation of medication. The uninjured eyes were accepted as the control group., Results: The corneal densitometry values at all zones of the posterior layer in the study eyes were significantly higher at the first week compared with the first month (P < 0.05 for all). Comparison of the corneal densitometry values of the study eyes at the first week with the fellow eyes showed significantly higher values at all zones of the posterior corneal layer (P < 0.05 for all). Comparison of the study eyes at the first month with the fellow eyes was significantly higher at the posterior 0- to 2-, 2- to 6-, and 6- to 10-mm zones (P = 0.030, P = 0.044, and P = 0.035, respectively). Although corneal densitometry values at the posterior 10- to 12-mm and posterior total zones were higher at the first month compared with those of the fellow eyes, these differences were not statistically significant (P = 0.197 and P = 0.085, respectively)., Conclusions: Corneal densitometry at all zones of the posterior corneal layer significantly changed after traumatic hyphema. Corneal densitometry analysis could be used in clinically normal cases for possible early corneal blood staining detection.

Purpose: To analyse the outcomes of keratoprosthesis in eyes with limbal stem cell deficiency (LSCD) and to compare the outcomes in two different keratoprosthesis devices., Methods: This was a single-centre retrospective comparative case series which included 81 eyes of patients with severe bilateral corneal blindness secondary to LSCD. The patients underwent either Boston type 1 keratoprosthesis (Boston Kpro, n=44) or Aurolab keratoprosthesis (AuroKpro, n=37) implantation. The primary outcome measures of anatomical retention and functional recovery of 20/200 or better visual acuity at yearly time points until 5 years of follow-up were compared between the two groups., Results: The most common indication overall was chemical injury (64.2%). Anatomical retention rates were similar in the Boston Kpro (30/44, 68.2%) and AuroKpro (23/37, 62.2%) groups (p=0.89). Kaplan-Meier survival rates at 5 years of follow-up were greater for the Boston Kpro group with respect to both anatomical retention (58.51%±9% vs 43.8±12%; p=0.23) as well as functional recovery (42.61%±8% vs 35.03±10%; p=0.9); these differences were not statistically significant. Overall, the most common complication was new-onset glaucoma (59%; 48/81). The difference in incidence rate of this complication was not statistically significant among the two groups (p=0.09)., Conclusion: Keratoprosthesis is an effective treatment option for patients with corneal blindness secondary to LSCD. In a setting where LSCD is a common cause of corneal blindness, the AuroKpro, when available can be considered an alternative to the Boston Kpro to achieve anatomical and functional success in patients who otherwise would not have access to this device., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Ectatic corneal disease (ECD) comprises a group of disorders characterized by progressive thinning and subsequent bulging of the corneal structure. Different phenotypes have been recognized, including keratoglobus, pellucid marginal degeneration (PMD), and keratoconus (KC). Keratoconus has been widely investigated throughout the years, but the advent of laser refractive surgery boosted an immediate need for more knowledge and research about ectatic diseases. This article discusses nomenclature of ectatic disease, etiology and pathogenesis, along with treatment options, with special focus ok KC and forme fruste keratoconus., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: To analyze the comparative safety and efficacy of two techniques of corneal neurotization (CN) (direct corneal neurotization [DCN] vs indirect corneal neurotization [ICN]) for the treatment of neurotrophic keratopathy (NK)., Design: Multicenter interventional prospective comparative case series., Methods: This study took place at ASST Santi Paolo e Carlo University Hospital, Milan; S.Orsola-Malpighi University Hospital, Bologna; and Santa Maria alle Scotte University Hospital, Siena, Italy. The study population consisted of consecutive patients with NK who underwent CN between November 2014 and October 2019. The intervention procedures included DCN, which was was performed by transferring contralateral supraorbital and supratrochlear nerves. ICN was performed using a sural nerve graft. The main outcome measures included NK healing, corneal sensitivity, corneal nerve fiber length (CNFL) measured by in vivo confocal microscopy (IVCM), and complication rates., Results: A total of 26 eyes in 25 patients were included: 16 eyes were treated with DCN and 10 with ICN. After surgery, NK was healed in all patients after a mean period of 3.9 months without differences between DCN and ICN. Mean corneal sensitivity improved significantly 1 year after surgery (from 3.07 to 22.11 mm; P < .001) without differences between the 2 groups. The corneal sub-basal nerve plexus that was absent before surgery in all patients, except 4, become detectable in all cases (mean CNFL: 14.67 ± 7.92 mm/mm 2 1 year postoperatively). No major complications were recorded in both groups., Conclusions: CN allowed the healing of NK in all patients as well as improvement of corneal sensitivity in most of them thanks to nerve regeneration documented by IVCM. One year postoperatively, DCN and ICN showed comparable outcomes., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background/aims: To evaluate long-term visual outcomes of Boston type I keratoprosthesis (KPro) surgery and identify risk factors for visual failure., Methods: Single surgeon retrospective cohort study including 85 eyes of 74 patients who underwent KPro implantation to treat severe ocular surface disease, including limbal stem cell deficiency, postinfectious keratitis, aniridia and chemical burns. Procedures were performed at the Centre hospitalier de l'Université de Montréal from October 2008 to May 2012. All patients with at least 5 years of follow-up were included in the analysis, including eyes with repeated KPro. Main outcome measures were visual acuity (VA), visual failure, defined as a sustained worse than preoperative VA, postoperative complications, and device retention., Results: Mean follow-up was 7.2±1.3 years (±SD). Mean VA was 2.1±0.7 (logarithm of minimal angle resolution) preoperatively and 1.9±1.2 at last follow-up. There were 2.4% of patients with VA better than 20/200 preoperatively and 36.5% at last follow-up. Maintenance of improved postoperative VA was seen in 61.8% of eyes at 7 years. Preoperative factors associated with visual failure were known history of glaucoma (HR=2.7 (1.2 to 5.9), p=0.02) and Stevens-Johnson syndrome (HR=7.3 (2.5 to 21.4) p<0.01). Cumulative 8-year complication rates were 38.8% retroprosthetic membrane formation, 25.9% hypotony, 23.5% new onset glaucoma, 17.6% retinal detachment, 8.2% device extrusion and 5.9% endophthalmitis. The majority (91.8%) of eyes retained the device 8 years after implantation., Conclusion: Almost two-thirds of patients had improved VA 7 years after KPro implantation. Preoperative risk factors for visual failure were known glaucoma and Stevens-Johnson syndrome., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To report the medium to long-term safety and performance outcomes of the KeraKlear nonpenetrating artificial cornea (KeraKlear) as the primary procedure in patients with corneal blindness due to noninflammatory anterior cornea disease., Methods: Fifteen patients with corneal blindness (preoperative visual acuity [VA] of ≥20/200) due to a non-inflammatory anterior corneal condition were included in this prospective, single-center study. Preoperative diagnoses included corneal scars, keratoconus, and corneal dystrophies. Diseased corneas were implanted with the KeraKlear (KeraMed Inc., Irvine, California, USA) by a single surgeon (JMV) using a femtosecond laser to create all incisions. Participants were followed up with for as long as 64 months. Uncorrected Snellen VA and postoperative complications were recorded., Results: The average age at the time of surgery was 49.6 years old and 67% of patients were female. The patients experienced an average improvement in uncorrected Snellen VA of 7.6 lines (-1.17 logMAR). Average uncorrected vision at the last visit was 20/100 (0.73 logMAR), and median uncorrected vision at the last visit was 20/70 (0.54 logMAR). One patient experienced extrusion of the KeraKlear due to infection. There were no cases of glaucoma, retroprosthetic membrane, or endophthalmitis, the three most common complications of penetrating keratoprostheses (KPro)., Conclusions: Medium and long-term outcomes of the KeraKlear indicate that this device is a viable alternative to corneal transplantation as a primary procedure in patients with non-inflammatory causes of corneal blindness, especially when corneal tissue is not available. The KeraKlear does not penetrate into the anterior chamber, and therefore, is less susceptible to the most common complications of penetrating KPro including endophthalmitis, glaucoma, and retroprosthetic membrane. The KeraKlear also has a comparable or improved adverse event rate compared to penetrating keratoplasty., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Middle East African Journal of Ophthalmology.)

The aim of this study is to determine the customized refractive index of ectatic corneas and also propose a method for determining the corneal and IOL power in these eyes. Seven eyes with moderate and severe corneal ectatic disorders, which had been under cataract surgery, were included. At least three months after cataract surgery, axial length, cornea, IOL thickness and the distance between IOL from cornea, and aberrometry were measured. All the measured points of the posterior and anterior parts of the cornea converted to points cloud and surface by using the MATLAB and Solidworks software. The implanted IOLs were designed by Zemax software. The ray tracing analysis was performed on the customized eye models, and the corneal refractive index was determined by minimizing the difference between the measured aberrations from the device and resulted aberrations from the simulation. Then, by the use of preoperative corneal images, corneal power was calculated by considering the anterior and posterior parts of the cornea and refractive index of 1.376 and the customized corneal refractive index in different regions and finally it was entered into the IOL power calculation formulas. The corneal power in the 4 mm region and the Barrett formula resulted the prediction error of six eyes within ± 1 diopter. It seems that using the total corneal power along with the Barrett formula can prevent postoperative hyperopic shift, especially in eyes with advanced ectatic disorders.

Purpose : To investigate the influence of chronic hyperglycemia in diabetes mellitus (DM) on spatial corneal thickness distribution and to analyze the influence of disease-specific factors. Methods : DM patients and healthy subjects were matched according to age and intraocular pressure (IOP). In diabetics, disease duration, DM type, and HbA 1c value were assessed. Spatially resolved corneal thickness was measured by Pentacam HR. Thinnest corneal thickness (TCT) and peripheral pachymetry of concentric circles around TCT were determined. The Dynamic Scheimpflug Analyzer Corvis ST (CST) was used to measure the parameter pachy slope, which is an indicator of the change of corneal thickness from the apex to the periphery. Results : 59 DM patients and 57 healthy subjects were included. Age ( P = .486) and IOP ( P = .154) were not different between the groups. In DM, pachy slope was significantly higher than in healthy subjects (41.1 ± 9.87 vs. 35.18 ± 10.64 μm, P = .004). Also, the differences between TCT and the average of peripheral corneal thickness of concentric circles with a diameter of 2 mm (10.3 ± 1.7 vs. 9.3 ± 3.8 μm, P < .001) to 6 mm (82.2 ± 12.4 vs. 76.8 ± 12.6 μm, P = .011) were increased in patients. Changes in thickness profile were associated with HbA 1c value and presence of diabetic retinopathy or maculopathy. Conclusion : In DM, a stronger peripheral corneal thickness increase was detectable. This change was shown using the novel CST parameter pachy slope and confirmed by Pentacam readings. These alterations might affect IOP and biomechanical measurements, and influence refractive procedures.

Purpose: To evaluate corneal morphology among patients with Wolfram syndrome (WFS)., Design: Comparative observational longitudinal case series of WFS patients with a laboratory approach in the WFS1 gene knockout (Wfs1KO) mouse model., Methods: A group of 12 patients with biallelic mutations in the WFS1 gene recruited from the whole country and a control group composed of 30 individuals with type 1 diabetes (T1D) were evaluated in a national reference center for monogenic diabetes. All subjects (n = 42) underwent a complete ophthalmic examination, computer videokeratography, and corneal thickness and endothelial measurements. Additionally, WFS patients (n = 9) underwent longitudinal videokeratography and Pentacam evaluation. Corneal characteristics were assessed and compared between both groups. Human and mouse corneas were subjected to immunohistochemistry to detect wolframin expression and microscopic evaluation to study corneal morphology ex vivo., Results: Clinical and topographic abnormalities similar to keratoconus were observed in 14 eyes (58.3%) of 8 WFS patients (66.7%). Flat keratometry, inferior-superior dioptric asymmetry, skewed radial axis, logarithm of keratoconus percentage index, index of surface variance, index of vertical asymmetry, keratoconus index, central keratoconus index, index of height asymmetry, and index of height decentration differed between WFS and T1D patients. Immunohistochemistry demonstrated wolframin expression in human and mouse corneas. Compared with Wfs1WT mice, Wfs1KO mice also presented corneal abnormalities., Conclusions: Patients with WFS present a high prevalence of changes in corneal morphology compatible with the diagnosis of early stages of keratoconus. Observations in a mouse model suggest that a mutation in the WFS1 gene may be responsible for corneal abnormalities similar to keratoconus., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Neurotrophic keratopathy (NK) produces persistent epithelial erosion which is hard to treat effectively. Recently, corneal neurotization surgery has produced reinnervation of the cornea with resolving neurotrophic keratopathy. We hypothesized that the generation of corneal epithelial nerves after neurotization surgery would not only restore the integrity of corneal epithelium but also produce a change in the configuration of the palisades of Vogt (POV), which houses the corneal epithelial stem cells., Methods: We assessed a patient with unilateral congenital corneal anesthesia with optical coherence tomography pre-neurotization and post-neurotization., Results: Over the course of 2 years, the patient gained corneal epithelial sensation and corneal and limbal epithelium was restored to normal thickness with corresponding changes in the POV., Conclusions: The intimate relationship between epithelium and sensory nerves of the cornea has been well documented; however, changes in the corneal epithelial stem cell niche in conjunction with development of innervation have not previously been reported. Considering the architecture of the corneal nerves in conjunction with the architecture of the POV may assist in developing treatments that can support the regeneration and maintenance of epithelium during nerve regeneration.

Purpose: To investigate whether cornea verticillata affects corneal topography, tomography, densitometry, or biomechanics of Fabry patients with ocular manifestations and to compare these results with those obtained from healthy subjects., Methods: This prospective, cross-sectional study included 23 Fabry patients (Fabry group) with cornea verticillata and the 37 age- and sex-matched healthy subjects (control group). After comprehensive ophthalmological examinations, corneal topography, tomography, and densitometry measurements were taken using Pentacam HR and corneal biomechanics were captured via Corvis ST for all participants., Results: All the investigated topographic and tomographic values were similar in the eyes with Fabry disease (FD) and the controls (P > 0.05). The corneal densitometry values of patients with FD were statistically significantly higher in all the concentric zones and layers, except posterior 0-2 mm and posterior 2-6 mm zones, compared to the controls (P < 0.05). The mean values of A1 velocity, A2 velocity, deformation amplitude ratio, Corvis biomechanical index, tomographic and biomechanical index, and Stiffness parameter at the first applanation in the Fabry group were statistically significantly different compared to control group (P < 0.05). However, the mean values of A1 length, A2 length, and the biomechanically corrected intraocular pressure were similar between the groups (P = 0.317, P = 0.819, and P = 0.468; respectively)., Conclusion: Although cornea verticillata associated with FD is not considered to affect vision, it is associated with increased light backscattering and reduced corneal transparency as well as altered corneal biomechanical properties.

Purpose : To evaluate the relationship between magnitude of orthokeratology (OrthoK) treatment zone decentration and 2-year axial length (AL) elongation in myopic children. Methods : One-hundred and one Chinese children who wore OrthoK contact lenses for 2 years. The magnitude and direction of the OrthoK treatment zone center from the entrance pupil center were recorded after 3 and 24 months of lens wear along with AL measurement. Stepwise multiple linear regression analysis was performed to assess which factors significantly affected an increase in AL. Results : After 3 and 24 months of OrthoK treatment, the mean (± standard deviation [SD]) magnitude of the OrthoK treatment zone decentration was 0.64 ± 0.38 mm and 0.68 ± 0.32 mm, respectively. There were no significant differences between the two time points ( P > .05). After 2 years of OrthoK contact lenses wear, the mean (± SD) AL growth was 0.36 ± 0.34 mm. The axial elongation was slightly correlated with baseline age of subjects (r = -0.073, P < .001), baseline spherical equivalent refractive error (r = -0.088, P < .001) and magnitude decentration of treatment zone (r = -0.190, P = .027). Conclusions : The decentration of OrthoK treatment zone stabilizes after 3 months of lens wear and slightly decreases AL growth.

The cornea is a transparent outermost structure of the eye anterior segment comprising the highest density of innervated tissue. In the process of corneal innervation, trigeminal ganglion originated corneal nerves diligently traverse different corneal cell types in different corneal layers including the corneal stroma and epithelium. While crossing the stromal and epithelial cell layers during innervation, due to the existing physical contacts, close interactions occur between stromal keratocytes, epithelial cells, resident immune cells and corneal nerves. Furthermore, by producing various trophic and growth factors corneal cells assist in maintaining the growth and function of corneal nerves. Similarly, corneal nerve generated growth factors critically modify the corneal cell function in all the corneal layers. Due to their close association and contacts, on-going cross-communication between these cell types and corneal nerves play a vital role in the modulation of corneal nerve function, regeneration during wound healing. The present review highlights the influence of different corneal cell types and growth factors released from these cells on corneal nerve regeneration and function.

Purpose: To determine patient-reported vision-related quality of life (VR-QoL) after Boston type I keratoprosthesis (BKPro) and its determinants., Methods: A cross-sectional study including consecutive consenting BKPro patients was conducted. The French National Eye Institute Visual Function Questionnaire-25 measured postoperative VR-QoL. Medical charts were retrospectively reviewed for demographics, ocular comorbidities, indication for surgery, postoperative visual acuity (VA), and complications. Univariate analyses were used to identify VR-QoL determinants. Multivariate linear regression was additionally performed for patients operated unilaterally, using VR-QoL as the dependent variable and age, sex, and postoperative VA as covariates. P < 0.05 indicated statistical significance., Results: Sixty-three patients, aged 63 ± 13 years, with a mean follow-up of 54 ± 19 months, were included. VR-QoL was measured 53 ± 18 months postoperatively. "Composite" VR-QoL scores in patients with unilateral (n = 51) and bilateral (n = 12) BKPro were 65 ± 23 and 63 ± 19, respectively, and did not significantly differ between the 2 groups (P = 0.71). In patients with unilateral BKPro, VR-QoL was determined by postoperative VA in the better eye, which was the contralateral nonoperated eye in most cases. Achieved vision in the operated eye contributed to VR-QoL when vision in the contralateral nonoperated eye was poorer. In the bilateral BKPro group, VR-QoL was determined by postoperative VA in the better eye and the number of ongoing complications., Conclusions: Five-year VR-QoL scores were lower in BKPro patients compared with healthy cohorts reported in the literature and were similar after unilateral and bilateral BKPro surgery. The main determinant of postoperative VR-QoL was postoperative vision in the better eye.

Purpose: To conduct a multimodal ophthalmic evaluation of systemic sclerosis (SSc) in patients using ocular response analyzer (ORA), Pentacam, and specular microscopy (SM)., Methods: Thirty-one SSc patients and a group of age- and sex-matched controls were enrolled in this cross-sectional study. Corneal hysteresis (CH), corneal resistance factor (CRF), corneal-compensated intraocular pressure (IOPcc), and Goldmann-correlated IOP (IOPg) were measured with ORA. Anterior chamber depth (ACD), central corneal thickness (CCT), and corneal volume (CV) measurements were obtained using Pentacam. Corneal endothelial cell density (ECD) and CCT were evaluated by SM., Results: SSc patients had significantly lower CH, ACD, and ECD values compared to the control group (p = 0.018; < 0.001; < 0.001, respectively). There was no significant difference regarding CRF, IOP, CV, or CCT measurements acquired by Pentacam and SM. Regarding CCT, SM and Pentacam showed relatively better agreement in SSc patients., Conclusions: Multimodal imaging can provide more comprehensive and useful information regarding the ocular involvement of systemic diseases. The multimodal evaluation in our study demonstrated that the pathologic effects of SSc may manifest as reductions in ACD, corneal elasticity, and ECD before there are any detectable changes in corneal thickness or IOP.

Background: To develop a method, using current clinical instrumentation, to estimate the Young's modulus of the human cornea in vivo., Methods: Central corneal curvature (CCC), central corneal thickness(CCT), intraocular pressure (IOP) was measured with the Goldmann tonometer (IOPG) and the Pascal Dynamic Corneal Tonometer(PDCT) in one eye of 100 normal young human subjects (21.07 ± 2.94 years) in vivo. The Orssengo and Pye algorithm was used to calculate the Young's modulus of the corneas of these subjects., Results: The Young's modulus(E) of the corneas of the subjects using the PDCT and IOPG results (Ecalc) was 0.25 ± 0.10MPa, and without the PDCT results (Eiopg) was 0.29 ± 0.06MPa. The difference in these results is due to the difference in tonometry results between the two instruments, as the mean PDCT result for the subjects was 16.89 ± 2.49mmHg and the IOPG result 15.06 ± 2.71mmHg. E was affected by the CCC of the subjects but more particularly by the CCT and IOP measurements. Corneal stiffness results are also presented., Conclusion: Two methods have been developed to estimate the Young's modulus of the human cornea in vivo using current clinical instrumentation. One method (Ecalc) is applicable to the general corneal condition, and Eiopg to the normal cornea, and these results can be used to calculate corneal stiffness., Competing Interests: The authors have declared that no competing interests exist.

Objectives: To assess the agreement of corneal power, corneal astigmatism, axis location, and astigmatic vector component measurements using a Lenstar LS900, a T-cone add-on, and an ARK 1S autorefractor, furthermore, to assess instrument agreement in a subset of astigmatic eyes., Methods: Retrospective analysis of keratometric readings from 3 instruments for 66 eyes undergoing cataract surgery at the Maryland Veterans Affairs Medical Center from November 2014 to 2015. Agreement in corneal power, mean corneal power, axis location, and astigmatic vector components (J0, J45) between devices was evaluated. Comparability was assessed using intraclass correlation, analysis of variance (ANOVA) one-way analysis, Bland-Altman analysis, and power vector analysis. Intraclass correlation was then assessed for a subset of 42 eyes with corneal astigmatism greater than or equal to 1 D., Results: The intraclass correlation between instruments was 0.941 for corneal power, 0.788 for corneal astigmatism, 0.932 for J0, and 0.809 for J45. The ANOVA one-way repeated P values comparing Kf, Ks, Km, corneal astigmatism, axis location, J0, and J45 were all greater than 0.05. Power vector analysis showed nearly all values between instruments to be within ±0.5 D. Finally, the intraclass correlation between instruments in eyes with ≥1 D of corneal astigmatism as measured by the T-cone was 0.946 for corneal power, 0.837 for corneal astigmatism, 0.948 for J0, and 0.950 for J45., Conclusions: The high level of agreement between all devices indicates the instruments may be used interchangeably. Our data suggest that this may also be true for the subset of eyes with greater than or equal to 1 D in astigmatism, highlighting the toric intraocular lens population.

Purpose: To determine the effect of the hormones estrogen and progesterone on the biomechanical properties of porcine corneas., Methods: Thirty fresh porcine corneas were acquired from an abattoir. The corneas were equally divided into three groups. Groups were incubated for 1 week in Eusol-C solution containing supra-physiologic concentrations of estrogen, progesterone, or control (no added hormone). After incubation, the central corneal thickness (CCT) of each cornea was measured using an electronic caliper, and then the corneas were cut into strips. The strips were then clamped in the pneumatic jaws of a computer-controlled biomaterial tester (Instron 4502, USA) and stretched at a constant rate of 1 mm/min until tissue rupture while constantly recording the stress and strain of the tissue. Stress-strain curves were plotted and Young's modulus was calculated for each corneal strip., Results: Average corneal thickness was 873.5 ± 143.1 μm for the control group, 928.0 ± 97.7 μm for the estrogen group, and 922.0 ± 116.7 μm for the progesterone group (data presented as mean ± SD). There was no statistically significant difference between the groups regarding the CCT (p = 0.89). The average Young's modulus was 17.00 ± 3.46 MPa for the control group, 16.95 ± 6.83 MPa for the progesterone group, and 12.33 ± 3.24 MPa for the estrogen group. The difference between the control and estrogen groups was statistically significant (p = 0.018) while the difference between the control and progesterone groups was not (p = 0.72)., Conclusion: Estrogen has a relaxing effect on the porcine cornea, resulting in reduced stiffness of the tissue. Progesterone has no significant effect on the biomechanical properties of porcine corneas. Estrogen and progesterone do not significantly affect CCT.

Purpose: To evaluate the visual function of patients with cornea verticillata associated with Fabry disease through quantitative evaluations of contrast sensitivity function and straylight., Methods: We enrolled 28 eyes of 14 patients with Fabry disease (mean age, 37.1 ± 17.2  years) and 20 eyes of 20 age-matched healthy controls. Comprehensive ophthalmological examinations were performed and contrast sensitivity and letter contrast sensitivity were measured for all patients, following which the area under the log contrast sensitivity function (AULCSF) was calculated. Straylight was quantified using a straylight metre. Furthermore, subgroup analysis was performed according to the whorl-like pattern of cornea verticillata (mild and typical groups)., Results: All 28 eyes showed cornea verticillata. Visual acuity and letter contrast sensitivity values were the same for normal eyes and those with Fabry disease. AULCSF differed by 0.15 log[s] between the eyes with Fabry disease and the control eyes (p < 0.001), while straylight differed by 0.45 log[s] between the two groups (p < 0.001). Subgroup analysis based on the whorl-like pattern of cornea verticillata showed that AULCSF and straylight differed by 0.11 log[s] and 0.08 log[s], respectively, between the typical and mild groups (p = 0.036 and p = 0.147, respectively)., Conclusion: Although cornea verticillata associated with Fabry disease does not affect the visual acuity and letter contrast sensitivity, more comprehensive testing of visual function by the inclusion of straylight and grating contrast sensitivity measurements shows clear functional deficits in these patients., (© 2019 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Aim: To report clinical outcomes and evidence of corneal innervation in patients with neurotrophic keratopathy (NK) treated with minimally invasive corneal neurotisation (MICN) using a sural nerve graft and donor sensory nerves from the face., Methods: Patients undergoing MICN at The Hospital for Sick Children, Toronto, Canada were prospectively recruited. Data on central corneal sensation (CCS, measured with Cochet-Bonnet aesthesiometer), best-corrected visual acuity (BCVA) and corneal epithelial integrity were collected. In four patients who subsequently underwent keratoplasty, immunohistochemical analysis was performed on the corneal explants. One patient underwent magnetoencephalography (MEG) after MICN to characterise the neurophysiological pathways involved., Results: Between November 2012 and February 2017, 19 eyes of 16 patients underwent MICN. Mean follow-up was 24.0±16.1 months (range, 6-53). Mean CCS significantly improved from 0.8±2.5 mm to 49.7±15.5 mm at final follow-up (p<0.001). Mean BCVA remained stable, and the number of episodes of corneal epithelial defects after MICN was significantly reduced compared with the year leading up to the procedure (21% vs 89%, respectively; p<0.0001). In the four eyes that underwent keratoplasties after MICN, all transplants fully re-epithelialised and regained sensation subsequently. Immunohistochemistry of the corneal explants demonstrated evidence of corneal reinnervation. In one patient who was 8 months after MICN, novel neuroactivity was detected on MEG in the ipsilateral somatosensory cortex on mechanical stimulation of the reinnervated cornea., Conclusions: By providing an alternative source of innervation, MICN improves corneal sensation and stabilises the corneal epithelium, permitting optical keratoplasty for patients with NK-related corneal opacity., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To determine the relative impact of contact lens- assisted corneal cross-linking (CACXL) and standard protocol CXL (CXL) on regional corneal stiffness using Brillouin microscopy., Methods: CXL and CACXL were performed on 30 intact fresh porcine eyes (15 per group). Depth profile of stiffness variation and averaged elastic modulus of anterior, middle, and posterior stroma were determined by Brillouin maps. Corneas were cut into strips to conduct mechanical stress-strain tests after Brillouin microscopy to evaluate stiffness difference between CXL and CACXL. Each eye served as its own control., Results: CXL had a greater impact on corneal stiffness, with a maximum increase of 5.74% compared to 3.99% for CACXL (P < .001). CXL increased longitudinal modulus by 7.8% in the anterior, 1.7% in the middle, and -0.7% in the posterior regions compared to CACXL, which increased longitudinal modulus by 5.5% in the anterior (P < .001), 1.2% in the middle (P = .15), and -0.4% in the posterior regions (P = .60). Mechanical stress-strain tests showed that at 10% strain averaged Young's modulus was 5 MPa for CXL and 2.97 MPa for CACXL (P < .001)., Conclusions: Both CACXL and standard protocol CXL induced significant corneal stiffening primarily concentrated in the anterior cornea. CACXL leads to less stiffening compared with CXL. An attenuated but continuous stiffening effect can be observed through the whole cornea for both CACXL and CXL, although CACXL has a smaller stiffness gradient. [J Refract Surg. 2019;35(11):721-728.]., (Copyright 2019, SLACK Incorporated.)

The cornea is the most sensitive structure in the human body. Corneal nerves adapt to maintain transparency and contribute to corneal health by mediating tear secretion and protective reflexes and provide trophic support to epithelial and stromal cells. The nerves destined for the cornea travel from the trigeminal ganglion in a complex and coordinated manner to terminate between and within corneal epithelial cells with which they are intricately integrated in a relationship of mutual support involving neurotrophins and neuromediators. The nerve terminals/receptors carry sensory impulses generated by mechanical, pain, cold and chemical stimuli. Modern imaging modalities have revealed a range of structural abnormalities such as attrition of nerves in neurotrophic keratopathy and post-penetrating keratoplasty; hyper-regeneration in keratoconus; decrease of sub-basal plexus with increased stromal nerves in bullous keratopathy and changes such as thickening, tortuosity, coiling and looping in a host of conditions including post corneal surgery. Functionally, symptoms of hyperaesthesia, pain, hypoaesthesia and anaesthesia dominate. Morphology and function do not always correlate. Symptoms can dominate in the absence of any visible nerve pathology and vice-versa. Sensory and trophic functions too can be dissociated with pre-ganglionic lesions causing sensory loss despite preservation of the sub-basal nerve plexus and minimal neurotrophic keratopathy. Structural and/or functional nerve anomalies can be induced by corneal pathology and conversely, nerve pathology can drive inflammation and corneal pathology. Improvements in accuracy of assessing sensory function and imaging nerves in vivo will reveal more information on the cause and effect relationship between corneal nerves and corneal diseases., (Copyright © 2019. Published by Elsevier Ltd.)

Limbal Stem Cell Deficiency (LSCD) is a painful and debilitating disease that results from damage or loss of the Corneal Epithelial Stem Cells (CESCs). Therapies have been developed to treat LSCD by utilizing epithelial stem cell transplants. However, effective repair and recovery depends on many factors, such as the source and concentration of donor stem cells, and the proper conditions to support these transplanted cells. We do not yet fully understand how CESCs heal wounds or how transplanted CESCs are able to restore transparency in LSCD patients. A major hurdle has been the lack of vertebrate models to study CESCs. Here we utilized a short treatment with Psoralen AMT (a DNA cross-linker), immediately followed by UV treatment (PUV treatment), to establish a novel frog model that recapitulates the characteristics of cornea stem cell deficiency, such as pigment cell invasion from the periphery, corneal opacity, and neovascularization. These PUV treated whole corneas do not regain transparency. Moreover, PUV treatment leads to appearance of the Tcf7l2 labeled subset of apical skin cells in the cornea region. PUV treatment also results in increased cell death, immediately following treatment, with pyknosis as a primary mechanism. Furthermore, we show that PUV treatment causes depletion of p63 expressing basal epithelial cells, and can stimulate mitosis in the remaining cells in the cornea region. To study the response of CESCs, we created localized PUV damage by focusing the UV radiation on one half of the cornea. These cases initially develop localized stem cell deficiency characteristics on the treated side. The localized PUV treatment is also capable of stimulating some mitosis in the untreated (control) half of those corneas. Unlike the whole treated corneas, the treated half is ultimately able to recover and corneal transparency is restored. Our study provides insight into the response of cornea cells following stem cell depletion, and establishes Xenopus as a suitable model for studying CESCs, stem cell deficiency, and other cornea diseases. This model will also be valuable for understanding the nature of transplanted CESCs, which will lead to progress in the development of therapeutics for LSCD., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose: To describe patterns of prescribing Prosthetic Replacement of Ocular Surface Ecosystem (PROSE) in irregular corneas and compare various components of lens design., Methods: Design: Retrospective, observational case series. 244 eyes of 173 patients with keratoconus (n=178), pellucid marginal degeneration (n=21), keratoglobus (n=6), following refractive surgery (n=19) and following keratoplasty (n=20) fitted with the PROSE device were retrospectively analyzed. Simulated keratometry value along the steep meridian (Steep-K) and anterior chamber depth (ACD) were measured using Scheimpflug imaging. Improvement in visual acuity and parameters of lens design such as vault, front surface eccentricity (FSE) and toricity were analyzed and compared across all conditions., Results: PROSE improved visual acuity, both uncorrected (median, 1.30 logMAR) and spectacle-corrected (median, 0.60 logMAR), to a median of 0.22 logMAR. Positive correlation was observed between Steep-K and ACD with lens vault, especially in keratoconus. Multiple regression analysis established ACD as the most reliable factor while choosing vault. FSE value of 0.6 was the most common across diagnostic subgroups. The distribution of FSE values did not differ between keratoconus patients with Steep keratometry of <60D or those >60D. In every diagnostic subgroup, at least 20% of eyes required a lens design of with-the-rule toricity of haptic., Conclusion: The PROSE device resulted in significant improvement in vision in this population. A trend of prescribing higher lens vault with increased keratometry value was evident especially in keratoconus. ACD appeared to be more important than Steep K in vault selection. An FSE of 0.6 and vertical peripheral lens toricity were used most frequently in this subset of patients., (Copyright © 2019. Published by Elsevier Ltd.)

Purpose: To compare the biomechanical properties of the unilateral operated corneas in patients who had undergone Descemet membrane endothelial keratoplasty (DMEK) for pseudophakic bullous keratopathy (PBK) with those of the contralateral normal corneas., Methods: This was a retrospective cohort study conducted at university hospitals (Department of Ophthalmology, Rabin Medical Center, Petach Tikva, Israel, and S. Fyodorov Eye Microsurgery State Institution, Moscow, Russia). Forty eyes of 20 patients who underwent DMEK for unilateral PBK 3.5 to 36 months ago and with normal fellow eyes were included in the study. An ocular response analyzer was used to measure the corneal biomechanical properties in the operated and normal fellow eyes. The main outcome measures were corneal hysteresis (CH) and corneal resistance factor (CRF)., Results: The mean CH (8.4 ± 1.5 mmHg vs. 8.2 ± 1.5 mmHg, P = 0.707) and the mean CRF (8.7 ± 1.6 mmHg vs. 8.3 ± 1.6 mmHg, P = 0.419) values did not show any statistically significant difference between the operated and the normal fellow eyes., Conclusions: In our study, the corneas that underwent DMEK for PBK showed normal values for biomechanical parameters. These findings support the previous studies that have reported near complete visual, functional, and ultra-structural rehabilitation of the corneas following DMEK.

Purpose: To evaluate, through the in vivo confocal microscopy, the pathological changes of each corneal layer in eyes affected by pseudoexfoliation syndrome., Methods: We studied 40 eyes of 40 patients with diagnosis of unilateral senile cataract associated with pseudoexfoliation syndrome and 40 eyes of 40 control subjects with senile cataract without pseudoexfoliation syndrome. All patients underwent a complete ophthalmic examination including best corrected visual acuity, slit-lamp examination, corneal sensitivity measurement using a Cochet-Bonnet nylon thread esthesiometer, and anterior segment optical coherence tomography (Visante OCT, Carl Zeiss Meditec AG, Germany); in vivo confocal microscopy of corneal sections (endothelium, stroma, sub-basal nerve plexus, and superficial and basal epithelium) was performed with the ConfoScan 4.0 (Nidek, Japan)., Results: In pseudoexfoliation syndrome group, the mean corneal sensitivity was 44.1 ± 1.3 mm and in the control group was 55.6 ± 4.7 mm. The corneas of the eyes with pseudoexfoliation syndrome were significantly less sensitive than those of control group eyes (p < 0.001). Pseudoexfoliation syndrome eyes had a lower nerve density and less nerve beadings and a higher degree of tortuosity in sub-basal plexus compared to the control group. The cell density of epithelial and endothelial layers was significantly lower in pseudoexfoliation syndrome eyes than controls. In 80% of pseudoexfoliation syndrome eyes, we found activated keratocytes and inflammatory cells in the anterior stroma., Conclusion: Our study demonstrates the morpho-structural corneal alterations in eyes affected by pseudoexfoliation syndrome, using corneal in vivo confocal microscopy as a non-invasive and high-reproducible technique to evaluate pathophysiology of each corneal layer; the sub-basal nerve plexus alterations are correlated with the lower corneal sensitivity.

Purpose: To evaluate and compare the influence of the wound healing process at the graft edge on corneal biomechanics after primary penetrating keratoplasty (PK) and repeat PK., Methods: This retrospective comparative study included 95 eyes: 35 eyes of 35 patients had PK, 40 eyes of 40 patients underwent repeat PK, and 20 eyes of 20 normal subjects served as the control group. The ocular response analyzer was used to measure and compare corneal hysteresis and corneal resistance factor among the study groups at least 6 months after all sutures were removed. In vivo confocal microscopy was used to study the corneal wound healing process at the graft edge in PK and repeat PK groups and to correlate these findings with corneal biomechanics., Results: Corneal hysteresis and corneal resistance factor were significantly lower in the PK group (6.71 ± 1.3 and 5.99 ± 1.2 mm Hg, respectively) as compared with the repeat PK group (9.4 ± 1.03 and 8.77 ± 1.1 mm Hg, respectively) (P < 0.0001). The repeat PK group demonstrated biomechanical parameters comparable with normal subjects (9.88 ± 1.29 and 9.24 ± 1.13 mm Hg, respectively) (P = 0.12). Confocal microscopy revealed more reflective and activated keratocytes at the graft edge in the repeat PK group as compared with the primary PK group., Conclusions: The healing process at the graft edge is the key to optimal corneal integrity after PK. Repeat PK stimulated more activated keratocytes than primary PK and hence a stronger healing response, providing superior corneal biomechanics comparable with normal subjects.

Purpose: To report the therapeutic effect of corneoscleral contact lenses (CLs) with a diameter of 14.0 mm on the refractory ocular surface diseases., Methods: Medical records of 13 eyes (of nine patients) attempted for fitting with corneoscleral CLs for the management of the severe refractory ocular surface diseases were retrospectively reviewed including Stevens-Johnson syndrome (SJS; eight eyes) and chronic ocular graft-versus-host disease (GVHD; five eyes). Lenses were fitted to improve refractory punctate epithelial erosions (PEE, ten eyes) and persistent epithelial defect (PED, three eyes with SJS) despite the proper medical management. Short-term (1 month) and long-term (12 months) changes in the best corrected visual acuity (BCVA), corneal fluorescein staining (CFS) score, mean wearing time, and National Eye Institute's Visual Function Questionnaire-25 (VFQ-25) were evaluated., Results: Of the 13 eyes, ten eyes were successfully fitted with the corneoscleral CLs. The fitting was failed in three eyes due to small palpebral fissure and shortened fornices (two eyes) and handling difficulty (one eye). At one-month follow-up after successful fitting in ten eyes, mean wearing time was 12.6 h (6.5-17, all day long) and BCVA improved from 0.56 ± 0.59 to 0.27 ± 0.46 in logMAR (P = .018). For the eight well-fitted eyes with refractory PEE, CFS score improved from 7.38±2.20 to 5.13±2.48 (P = .024). PED improved in all two eyes which were successfully fitted with corneoscleral CLs (Of the three eyes with PED, one eye failed fitting). At 12-month follow-up, mean wearing time was 11.4 h and the improved BCVA and CFS score were maintained. Furthermore, no adverse events attributable to corneoscleral CLs use occurred., Conclusion: The corneoscleral CLs with a diameter of 14.0 mm were successfully fitted in ten out of 13 eyes with severe refractory ocular surface diseases and demonstrated therapeutic benefits in the well-fitted eyes. The corneoscleral CL can be an option in the management of severe refractory ocular surface diseases., (Copyright © 2018. Published by Elsevier Ltd.)

The cornea is a valuable tissue for studying peripheral sensory nerve structure and regeneration due to its avascularity, transparency, and dense innervation. Somatosensory innervation of the cornea serves to identify changes in environmental stimuli at the ocular surface, thereby promoting barrier function to protect the eye against injury or infection. Due to regulatory demands to screen ocular safety of potential chemical exposure, a need remains to develop functional human tissue models to predict ocular damage and pain using in vitro-based systems to increase throughput and minimize animal use. In this review, we summarize the anatomical and functional roles of corneal innervation in propagation of sensory input, corneal neuropathies associated with pain, and the status of current in vivo and in vitro models. Emphasis is placed on tissue engineering approaches to study the human corneal pain response in vitro with integration of proper cell types, controlled microenvironment, and high-throughput readouts to predict pain induction. Further developments in this field will aid in defining molecular signatures to distinguish acute and chronic pain triggers based on the immune response and epithelial, stromal, and neuronal interactions that occur at the ocular surface that lead to functional outcomes in the brain depending on severity and persistence of the stimulus., (Copyright © 2018. Published by Elsevier Ltd.)

Purpose of Review: Neurotrophic keratopathy is a devastating corneal condition that can lead to ocular morbidity and blindness. Current medical and surgical treatments poorly tackle the essential problem of corneal aesthesia and hence fail to provide a permanent cure. Recent advances in corneal neurotization techniques have shown promise to restore corneal nerves in neurotrophic keratopathy. This article aims at reviewing the current surgical advances, along with the current thoughts and evidence available for corneal nerve regeneration., Recent Findings: Corneal neurotization was first introduced in 2009 by Terzis et al., but recently picked up more interest since 2014. Direct and indirect neurotization are being developed, and different nerves (sural nerve, great auricular nerve) have been explored for interposition between frontal nerve branches and the cornea. New endoscopic techniques are introduced for less invasive approaches. On the corneal front, confocal microscopy and esthesiometry studies have established that the regeneration of the corneal nerves is happening 6 months after the procedure., Summary: Neurotization is a budding revolutionary technique that shows promise of cure for neurotrophic corneas, but at this stage, it is still reasonably invasive and still reserved for selected patients.

Purpose: To compare corneal biomechanics between patients with ocular graft versus-host disease (oGVHD) and healthy subjects (controls), and to further correlate these values with ocular and hematological characteristics., Materials and Methods: The following procedures were performed in oGVHD patients and controls: Schirmer test (ST), break-up time (BUT), corneal and conjunctival staining, tear matrix metalloproteinase-9 (MMP-9) assay (InflammaDry test, Rapid Pathogen Screening, Inc, Sarasota, FL). Corneal biomechanics were calculated by using ocular response analyzer (ORA, Reichert Instruments, Depew, New York, USA). The Mann-Whitney U test was used to compare continuous variables between oGVHD patients and controls. Correlations of corneal biomechanics with ocular and hematological parameters were examined using Spearman's correlation., Results: A total of 45 oGVHD patients (mean age ± SD, 51.5 ± 7.1 years) and 34 controls (47.8 ± 6.1 years) were included. Patients with oGVHD showed significantly lower values of corneal hysteresis (CH) and corneal resistance factor (CRF) compared to controls (respectively, 9.4 ± 1.8 mmHg vs 11.6 ± 1.6 and 9.7 ± 1.4 mmHg vs 12.3 ± 1.3; always p<0.001). Twenty-nine of the oGVHD eyes (64.4%) were strong-positive for MMP-9, while 16 (35.6%) were weak-positive. Conversely, only 4 of the control eyes (11.8%) were weak-positive for MMP-9. In patients with oGVHD, CH was significantly correlated with corneal staining (Rs = -0.316, p = 0.035), conjunctival staining (Rs = -0.437, p = 0.003), ST (Rs = 0.390, p = 0.008), BUT (Rs = 0.423, p = 0.004), oGVHD severity grade (Rs = -0.383, p = 0.009), and MMP-9 positivity grade (Rs = -0.429, p = 0.003), while CRF was correlated only with corneal staining (Rs = -0.317, p = 0.034)., Conclusions: Corneal biomechanics are reduced in patients with oGVHD, and CH is negatively correlated with disease severity grade and MMP-9 tear levels., Competing Interests: The authors have declared that no competing interests exist.

During the last 2 decades, modifying the shape of the cornea by means of laser photoablation has emerged as a successful and popular treatment option for refractive errors. Corneal surface ablation techniques such as photorefractive keratectomy (PRK) and laser-assisted subepithelial keratomileusis (LASEK) offer good refractive results while having a minimal impact on corneal biomechanical stability. Past limitations of these techniques included the long-term regression of refractive outcome and a vigorous healing response that reduced corneal clarity in some patients (giving rise to what is clinically described as "haze"). Mitomycin C (MMC) was introduced as a healing modulator and applied on the corneal surface after refractive surgery to address these drawbacks. This article critically reviews the available evidence on the biological effects, safety, and clinical benefits of the off-label use of MMC in corneal refractive surgery.

Corneal nerves are key components of the physiological system that controls ocular surface homeostasis. The cornea is primarily innervated by the ophthalmic branch of the trigeminal nerves (cranial nerve V), which distend bilaterally from the pons. The nasociliary branch (afferent) of the ophthalmic nerve is sensory for cornea, eyelid and conjunctiva. These nerve fibres play a role in sensing temperature, chemical and mechanical stimuli, and pain, whereas, branches of the facial nerve (cranial nerve VII) contain motor nerves that control blinking and autonomic (sympathetic and a paucity of parasympathetic) fibres that stimulate tear production and secretion via feedback loops between the ocular surface, lacrimal glands and brain. Disruption of these nerves with interruption of neural feedback loops between the ocular surface and lacrimal glands can lead to corneal diseases such as dry eye disease (DED) and neurotrophic keratopathy (NK). Inversely, hypersensitivity of the nerve fibres and/or dysregulation of pain-controlling nervous centres may lead to neuropathic pain. Recently, medications that specifically target regeneration of corneal nerves have started to become available - and considering the high prevalence of diseases associated with corneal nerve dysfunction, these agents promise to fulfil a hitherto important unmet need. In this review, we explore the physiology of corneal nerves, the pathology of corneal nerve diseases and how these relate to neuropathic pain, NK and DED. We also discuss what novel treatments may be useful against diseases involving corneal nerves., (© 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: This study compares the corneal biomechanical properties, as measured with Corvis ST, in three groups of cases with delayed-onset mustard gas keratopathy (DMGK), chronic corneal scarring (CCS), and those with normal corneas., Methods: Forty-five eyes were enrolled in the DMGK, CCS, and normal groups (15 eyes each). All patients were examined with the slitlamp and Corvis ST. Extracted corneal biomechanical parameters included first and second applanation time (AT1, AT2), first and second applanation length (AL1, AL2), first and second applanation velocity (AV1, AV2), deformation amplitude (DA), highest concavity time, peak distance, highest concavity radius (HCR), central corneal thickness, corrected intraocular pressure (IOP), and noncorrected IOP., Results: The mean age of the participants in the DMGK, CCS, and normal groups was 49.20±5.16, 60.40±22.92, and 44.60±8.32 years, respectively. Comparison between DMGK and CCS groups showed significant differences in AT1, AT2, corrected IOP, and noncorrected IOP. There were also significant differences in AT1, AT2, HCR, DA, and noncorrected IOP between the DMGK and normal groups. None of the parameters were significantly different between the CCS and normal groups., Conclusion: There seems to be reduced corneal rigidity and stiffness in cases exposed to mustard gas, which causes the cornea in the DMGK group to become applanated more easily and take longer to rebound compared with the other two groups. Also, IOP was lower than normal in the DMGK group, and thus, misdiagnosis of glaucoma is likely for these patients.

Purpose:: To analyze and correlate corneal parameters with refractive shift after Descemet membrane endothelial keratoplasty combined with cataract surgery (triple Descemet membrane endothelial keratoplasty)., Methods:: This single-center retrospective observational case series included 152 eyes of 152 consecutive patients undergoing triple Descemet membrane endothelial keratoplasty in the first eye for Fuchs endothelial corneal dystrophy. Patients were examined preoperatively, as well as at 3, 6, and 12 months after surgery. The main outcome measures were: refractive shift (predicted refractive outcome based on intraocular lens calculation compared to actual postoperative refractive outcome), central corneal thickness, corneal volume, anterior and posterior corneal curvature, and corneal densitometry. These parameters were analyzed and correlated with the refractive shift after surgery., Results:: After 3 months from surgery, a mean refractive shift of +1.12 ± 1.10 D was observed and remained stable until the last follow-up at 12 months (+1.24 ± 1.07 D). Correlation analysis showed a weak but significant positive correlation between refractive shift and preoperative posterior curvature (rho = 0.314; p = 0.002) or preoperative posterior densitometry (rho = 0.227; p = 0.008). No correlation was found between refractive shift and preoperative central corneal thickness, corneal volume, anterior curvature, or anterior/mid-cornea densitometry., Conclusion:: Changes of the posterior cornea may have an influence on the refractive shift. Patients with flatter posterior corneal curvature or higher posterior corneal density seem to exhibit a higher hyperopic shift. The weak correlations indicate a poor predictive value of any preoperative parameter used in our study.

Purpose: To evaluate whether and how preoperative visual acuity predicts visual acuity outcome after Descemet Membrane Endothelial Keratoplasty (DMEK)., Methods: One thousand eighty-four out of 1162 consecutive eyes having undergone DMEK alone or combined with cataract surgery (triple-DMEK) between July 2011 and February 2016 from the prospective Cologne DMEK database were included and analyzed retrospectively for correlations between pre- and postoperative visual acuity values at 1, 3, 6, and 12 months after transplantation., Results: There is a significant correlation between pre- and postoperative visual acuity (VA) after (triple)-DMEK after 6 and 12 months (p = 0.005 and p = 0.011 respectively; Pearson's correlation coefficient 0.240 and 0.224). Preoperative VA below 20/100 leads to delayed and reduced final visual acuity results after 12 months (p < 0.001). However, defining an increase in VA > 0.1 logMAR as clinically relevant, we could not show any clinically relevant significant difference in the time needed to recover to final VA and in final VA. There is no significant difference for preoperative VA values above 20/40. The chance to reach postoperative VA above 20/25 is 40% for preoperative VA of 20/200, 50% for preoperative VA of 20/60 and > 60% for preoperative VA of 20/40., Conclusion: DMEK results in very good final postoperative visual acuity results even in eyes with very poor preoperative vision caused by corneal pathology. However, preoperative visual acuity values below 20/100 result in significantly poorer visual recovery, which suggests that there is benefit in performing surgery early enough before this value is reached. Preoperative visual acuity seems to be an adjuvant tool for the prediction of the final visual outcome after DMEK.