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To evaluate the intermediate-term clinical outcomes of Rose Bengal Photodynamic Antimicrobial Therapy (RB-PDAT) for infectious keratitis; secondarily, to evaluate the surgical outcomes of individuals who underwent optical keratoplasty after RB-PDAT.Retrospective cohort study.A retrospective chart review was performed of 31 eyes from 30 consecutive individuals with infectious keratitis refractory to standard medical therapy who underwent RB-PDAT at the Bascom Palmer Eye Institute between January 2016 and July 2020. Data collected included demographics, risk factors for infectious keratitis, microbiological diagnosis, best spectacle-corrected visual acuity (BCVA), clinical outcomes after RB-PDAT, and complication rates post-keratoplasty. RB-PDAT was performed as described in previous studies. Graft survival was evaluated using Kaplan-Meier curves with log-ranks in individuals who underwent keratoplasty after RB-PDAT.The mean age of the study population was 53 ± 18.0 years. In all, 70% were female; 53.3% self-identified as non-Hispanic White and 43.3% as Hispanic. Mean follow-up time was 28.0 ± 14.4 months. Risk factors included contact lens use (80.6%), history of infectious keratitis (19.3%), and ocular surface disease (16.1%). Cultures were positive for Acanthamoeba (51.6%), Fusarium (12.9%), and Pseudomonas (6.5%). Of the individuals with Acanthamoeba infection, 22.5% were treated with concomitant Miltefosine. Clinical resolution was achieved in 77.4% of patients on average 2.72 ± 1.85 months after RB-PDAT, with 22.5% requiring therapeutic penetrating keratoplasties and 54.8% subsequently requiring optical penetrating keratoplasties. At 2 years, the overall probability of graft survival was 78.7%, and the graft failure rate was 21.3%.RB-PDAT is a potential adjunct therapy for infectious keratitis that may reduce the need for a therapeutic penetrating keratoplasty. Patients who undergo keratoplasty after RB-PDAT may have a higher probability of graft survival at 1 year postoperatively.

PURPOSE OF REVIEW: To review the existing literature and investigate the role of microbiologic culture and histopathologic examination of corneal biopsies in the management of infectious keratitis. RECENT FINDINGS: Corneal biopsy continues to be a significantly useful tool in the diagnosis and tailored management of infectious keratitis. Several techniques can be employed for tissue collection, handling, and processing to optimize diagnostic yield and maximize safety, including emerging femtosecond laser-assisted biopsy. SUMMARY: Corneal opacities represent a significant cause of global blindness, and infectious keratitis is the most common etiology. Organism identification in progressive infectious keratitis is essential for proper management. However, microbiological culture alone has a high rate of false-negative results. Records from the Bascom Palmer Eye Institute were retrospectively searched for patients between January 1, 2015, and December 31, 2019, who underwent corneal biopsy, therapeutic keratoplasty, or endothelial graft removal for infectious keratitis and had specimens bisected and submitted for evaluation with both microbiologic culture and histopathologic examination. Detection of bacteria, fungus, and mycobacteria was not statistically different between culture and histopathology. Microbiology and histopathology are complementary methods for the identification of causative microorganisms in corneal specimens with presumed infectious keratitis.

A healthy middle-aged man sustained extensive burns after a motor vehicle accident, including fourth-degree burns to the ocular adnexa. He had bilateral eyelid necrosis with complete tissue loss to the orbital rim. Progressive corneal thinning occurred bilaterally despite frequent lubrication, weekly amniotic membrane placement, and a Gunderson flap, ultimately requiring evisceration of his OS. In accordance with family wishes to perform all interventions for the OD, he underwent ocular surface reconstruction with levator palpebrae superioris (LPS) and inferior oblique (IO) muscle flaps, supplemented with an orbital fat transfer and bucket-handle muscle flap. These flaps were covered with porcine urinary bladder matrix and remained viable with complete globe coverage postoperatively. Although local eyelid flaps traditionally involve tissue supplied by branches of the external carotid artery, this case suggests that orbital-internal carotid artery based flaps utilizing the LPS and IO muscles may achieve ocular surface coverage after complete periocular and facial soft tissue loss.

An exhaustive search of the world's literature was performed to analyze all case reports and series on the modified osteo-odonto-keratoprosthesis (MOOKP) published up to January 2022. The demographic profile, the primary indication for surgery, surgical technique variations, postoperative medical management, long-term functional and anatomical outcomes, and intra- and postoperative complications were analyzed and compared. Additionally, some of the authors' (GI, VP, and GA) unpublished MOOKP cases were studied. An extensive literature search yielded 37 case series and case reports. Overall, 958 patients were analyzed. The most common indication for surgery was autoimmune disease (39.1%), closely followed by chemical injury (38.8%). The most common intraoperative complications (21.67%) included maxillofacial, vitreous hemorrhage/vitritis, and mucosal. The most common postoperative complications (78.4%) were lamina and oral mucosa-associated, secondary glaucoma, and choroid/retinal detachment. Follow-up periods ranged from one to 364 months (median: 36.7 months). Altogether, 78% of patients achieved a visual acuity of 20/400 or better at the end of the follow-up period, and 91.2% improved at least temporarily after MOOKP surgery. Mean anatomic success at the end-of-follow-up for all patients was 88.25% (range, 50-100%). The long-term anatomic and functional success of the MOOKP makes it a reliable option for visual rehabilitation in patients with bilateral corneal blindness and end-stage ocular surface disease. This review aims to describe the evolution of the MOOKP procedure, analyzing all published case series for its long-term reliability, visual and anatomical outcomes, complications, and future directions.

PURPOSE The purpose of this study was to report the indications, ocular and systemic comorbidities, and surgical outcomes of corneal transplantation in patients older than 90 years. METHODS A retrospective review was conducted to identify individuals 90 years and older who underwent corneal transplantation surgery at the Bascom Palmer Eye Institute between January 2013 and October 2020. Outcomes included best-corrected visual acuity and graft survival over time. Paired t tests were used to compare visual acuity preoperatively versus postoperatively. Graft survival was evaluated with Kaplan-Meier curves. RESULTS Fifty-eight eyes of 52 consecutive individuals were included. The mean age of individuals was 92 ± 2 years; 26.9% were male; and 48.1% self-identified as non-Hispanic White and 38.5% as Hispanic. Postoperative follow-up was 14.7 ± 12.1 months. Of the 58 eyes, 44.8% (26/58) underwent penetrating keratoplasty, 46.6% (27/58) Descemet stripping automated endothelial keratoplasty, and 6.9% (4/58) keratoprosthesis. All surgeries were performed under monitored local anesthesia, without major complications. Surgical indications included pseudophakic bullous keratopathy (36.2%), glaucoma-associated corneal decompensation (27.6%), Fuchs endothelial dystrophy (25.9%), and perforated corneal ulceration (19.0%). The best-corrected visual acuity improved by 0.32 (95% confidence interval 0.14-0.50; P < 0.01) as early as 1 month postoperatively, and vision gains were sustained for at least 12 months. Graft survival probability at 12 months was 88%. CONCLUSIONS Corneal transplantation is a safe and successful procedure in restoring the visual acuity for patients older than 90 years after careful preoperative evaluation. Further research is needed to evaluate the impact of corneal transplantation on quality of life in patients in the 10th decade of life.

There is a need to understand physicians' diagnostic uncertainty in the initial management of microbial keratitis (MK). This study aimed to understand corneal specialists' diagnostic uncertainty by establishing risk thresholds for treatment of MK that could be used to inform a decision curve analysis for prediction modeling.A cross-sectional survey of corneal specialists with at least 2 years clinical experience was conducted. Clinicians provided the percentage risk at which they would always or never treat MK types (bacterial, fungal, herpetic, and amoebic) based on initial ulcer sizes and locations (2 mm2 central,2 mm2 peripheral, and8 mm2 central).Seventy-two of 99 ophthalmologists participated who were 50% female with an average of 14.7 (SD = 10.1) years of experience, 60% in academic practices, and 38% outside the United States. Clinicians reported they would "never" and "always" treat a2 mm2 central MK infection if the median risk was 0% and 20% for bacterial (interquartile range, IQR = 0-5 and 5-50), 4.5% and 27.5% for herpetic (IQR = 0-10 and 10-50), 5% and 50% for fungal (IQR = 0-10 and 20-75), and 5% and 50.5% for amoebic (IQR = 0-20 and 32-80), respectively. Mixed-effects models showed lower thresholds to treat larger and central infections (P0.001, respectively), and thresholds to always treat differed between MK types for the United States (P0.001) but not international clinicians.Risk thresholds to treat differed by practice locations and MK types, location, and size. Researchers can use these thresholds to understand when a clinician is uncertain and to create decision support tools to guide clinicians' treatment decisions.

To describe the long-term management of bilateral limbal stem cell deficiency secondary to a severe chemical burn.Descriptive case report.This case highlights the importance of early intervention in ocular chemical burns for the preservation of tissue integrity and avoidance of perforation. We also review the use of proper ocular surface reconstructive techniques to restore the function of the limbal area, as well as the immunomodulatory strategies and follow-up needed for these interventions.

This case report describes severe multidrug-resistant Pseudomonas aeruginosa keratitis in a 72-year-old man after EzriCare artificial tear use.

Purpose To evaluate the in vivo corneal changes after Rose Bengal photodynamic antimicrobial therapy (RB-PDAT) treatment in New Zealand White rabbits. Methods Sixteen rabbits were divided into 5 groups. All groups underwent deepithelialization of an 8 mm diameter area in the central cornea. Group 1: balanced salt solution drops only, group 2: 0.2% RB only, group 3: green light exposure (525 nm, 5.4 J/cm2) only, group 4: 0.1% RB-PDAT, and group 5: 0.1% RB-PDAT. All rabbits were followed clinically. Group 5 rabbits were followed using anterior segment optical coherence tomography (AS-OCT) and clinically. On day 35 after initial treatment, 1 rabbit from group 5 was re-exposed to green light (5.4 J/cm2) to evaluate reactivation of the remaining RB dye, and terminal deoxynucleotyl transferase-mediated UTP-biotin-nick-end labeling assay was performed on corneal cryosections. Results Complete reepithelization was observed, and corneas remained clear after treatment in all groups. In group 5, AS-OCT revealed a cross-linking demarcation line. AS-OCT showed RB fluorescence and collagen cross-linking in all treated eyes of group 5 animals after 5 weeks of treatment. Photobleached RB retention in the corneal stroma was corroborated by fluorescence confocal microscopy on frozen sections. There was no evidence of a sustained cytotoxic effect through terminal deoxynucleotyl transferase-mediated UTP-biotin-nick-end labeling at 5 weeks. Conclusions RB-PDAT with 0.1% RB is a safe procedure. There was no difference clinically and on histopathology compared with control groups. In eyes where RB dye is retained in the corneal stroma after 1 month of treatment, oxidative stress is not evidenced at long term.

Purpose To report the unexpected finding of ocular surface neoplasia (OSSN) on conjunctival tissue removed during pterygium surgery and subjected to histopathology analysis. Methods This is an observational, descriptive retrospective study in which all the samples removed during surgery between 1997 and 2020 with a clinical diagnosis of pterygium were sent for histopathology analysis in which an unexpected OSSN was found. Results There were 461 cases with a preoperative diagnosis of pterygium, with a mean age of 30.14 ± 10.6 years. In this group, there was an unexpected finding of OSSN in 69 cases (14.96%) of the surgical samples, with a mean age of 46 ± 8.2 years (31.86 ± 12.13). Conclusions The unexpected coincidence of pterygium and OSSN is frequent, although varies depending on the geographical location. We recommend performing a histopathology analysis on every pterygium removed.

To report photokeratitis caused by the improper use of germicidal lamps purchased during the COVID-19 pandemic.Case series.Seven patients presented with acute ocular surface pain after exposure to UV-emitting germicidal lamps. Visual acuity was 20/30 or better in 13 of 14 eyes (93%). Anterior segment examination revealed varying degrees of conjunctival injection and diffusely distributed punctate epithelial erosions (PEEs) in every patient. No intraocular inflammation was identified across the cohort and all fundus examinations were normal. Treatment varied by provider and included artificial tears alone or in combination with antibiotic ointments and/or topical steroids. Five patients were followed via telehealth, one patient returned for an in-office visit, and one patient was lost to follow-up. Five of six patients endorsed complete resolution of symptoms within 2-3 days.Patients should follow manufacturer recommendations when using UV-emitting germicidal lamps and avoid direct exposure to the ocular surface.

AimTo report the clinical outcomes of autologous minor salivary gland transplantation (MSGT) for the treatment of severe dry eye disease caused by cicatrising conjunctivitis.MethodsThis was a retrospective case series of patients undergoing MSGT at four different centres from 2016 to 2018. The technical modifications included en bloc harvesting of a 20 mm×15 mm mucosa–gland–muscle complex and fixation of the glands to the superior bulbar surface anchored to the superior rectus muscle. The primary outcome measure was improvement in best-corrected visual acuity (BCVA). Secondary outcome measures were change in Schirmer test scores and grades of conjunctival and corneal fluorescein staining, grades of corneal neovascularisation, opacification and keratinisation.Results21 eyes of 19 patients underwent MSGT, with a median follow-up duration of 3 years. The median BCVA improved from a baseline value of 20/500 to 20/125 at 1 year (p=0.0004) and 20/80 at 3 years (p=0.0002) after surgery. The proportion of cases with BCVA ≥20/200 improved from 38% at baseline to 67% at 1 year (p=0.0294), 78% at 2 years (p=0.0227) and 93% at 3 years (p=0.0015) after surgery. There was a significant improvement (pConclusionsLong-term improvement in the visual acuity, ocular surface environment, and keratopathy was noted after MSGT performed in severely dry eyes using a modified technique.

A 79-year-old man presented to a tertiary referral center from the Dominican Republic with an opaque corneal graft and a diagnosis of chronic, recurrent culture-positive Achromobacter xylosoxidans endophthalmitis of the left eye. The patient had a history of penetrating keratoplasty for Fuchs' dystrophy and had undergone multiple intraocular surgeries including pars plana vitrectomy and anterior chamber wash out for the diagnosis and management of chronic endophthalmitis. After being referred, the patient underwent a third PKP, removal of his intraocular lens (IOL), capsulectomy, and injection of intravitreal antibiotics. All surgical specimens demonstrated the growth of A. xylosoxidans. Five months after surgery, the graft remained clear without evidence of infection and best-corrected visual acuity was 20/350.

To report our experience with oral miltefosine (MLT) as an adjunct treatment for progressive Acanthamoeba keratitis (AK).Retrospective case series of all patients who underwent treatment with oral ...

The purpose of this study was to assess the role of combined surgical treatment of therapeutic penetrating keratoplasty and pars plana vitrectomy in the anatomical and functional outcome of infectious keratitis endophthalmitis.This study reviewed the medical records of 4 participating centers in the United States and Mexico. This study included patients with a clinical diagnosis of infectious keratitis endophthalmitis who had been treated with an early therapeutic penetrating keratoplasty and pars plana vitrectomy as the main treatment for endophthalmitis. From each medical record, the study retrieved demographic data, relevant medical and drug history, baseline clinical manifestation of endophthalmitis, best-corrected visual acuity, and the need for enucleation/evisceration for the control of the infection or any other reason through the follow-up.The study included 48 patients (50.15 ± 20.6 years). The mean follow-up time was 13 ± 0.5 months. The mean best-corrected visual acuity at baseline was 2.1 ± 0.25 logarithm of the minimum angle of resolution. At month 12 was 2.09 ± 0.61 logarithm of the minimum angle of resolution (P = 0.9). The overall prevalence of enucleation/evisceration was 8.3% (95% confidence interval: 2.32%-19.98%). The prevalence of a vision of no-light perception was 20.8% (95% confidence interval: 2.32%-19.98%).Combined surgery for severe cases of infectious keratitis endophthalmitis eradicates the infection in most cases, while significantly improving the overall outcomes.

Purpose To describe the outcome of simple limbal epithelial transplantation along with Phacoemulsification and IOL implantation for visual rehabilitation in limbal stem cell deficiency due to ocular surface squamous neoplasia. Observations This case report of a 66-year-old woman clinically diagnosed with OSSN in her right eye involving all cornea and limbus meridians. Topical chemotherapy for tumor treatment was done, followed by SLET and sequential cataract surgery. The entire tumor could be clinically reduced with topical chemotherapy but a LSCD could not be avoided. After SLET, corneal transparency was restored, and anterior segment details could be seen, phacoemulsification was performed uneventfully. After a follow-up period of 18 months, stable ocular surface and visual acuity and no tumor recurrence was observed. Conclusions SLET is an option to restore not only corneal epithelium homeostasis but also gain cornea transparency, avoid keratoplasties and allow anterior segment surgeries to be performed. Importance This case report provide evidence of benefits of simple limbal epithelial transplantation in ocular surface squamous neoplasia and shows that cataract surgery could be performed uneventfully after limbal stem cell transplantation.

Toxic anterior segment syndrome is a surgical complication characterized by a noninfectious anterior chamber inflammatory reaction having multiple etiologies. The clinical signs (prominent limbus-to-limbus corneal edema, anterior chamber inflammation) and symptoms (decreased visual acuity, discomfort) generally occur within the first 12-48 hours after intraocular surgery. Most patients achieve good clinical and visual outcomes when there is a prompt clinical diagnosis and adequate treatment. We review the literature on toxic anterior segment syndrome, emphasizing its etiology, pathophysiology, and clinical and surgical management, as well as prognosis and sequelae. Our goal is to reduce the frequency of toxic anterior segment syndrome by highlighting the importance of prevention, early recognition, and distinguishing toxic anterior segment syndrome from infectious endophthalmitis.

Jeffrey C Peterson,1,2 Heather Durkee,1,2 Darlene Miller,3,4 Jorge Maestre-Mesa,3,4 Alejandro Arboleda,1 Mariela C Aguilar,1 Nidhi Relhan,1 Harry W Flynn Jr,3 Guillermo Amescua,3 Jean-Marie Parel,1–3 Eduardo Alfonso3 1Ophthalmic Biophysics Center, Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA; 2Department of Biomedical Engineering, University of Miami, Coral Gables, FL, USA; 3Anne Bates Leach Eye Center, Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA; 4Ocular Microbiology Laboratory, Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA Purpose: To characterize the molecular, epidemiological, and resistance profiles of methicillin-resistant (MRSA) and methicillin-susceptible (MSSA) keratitis isolates.Patients and methods: We used a combination of standard microbiological techniques and DNA microarray analysis to characterize the molecular and antibiotic resistance profiles of 75 Staphylococcus aureus keratitis isolates collected over an 11-year period (2006–2016).Results: Two major USA clonal complexes (CC), CC5 (n=30, 40%) and CC8 (n=28, 37.3%), accounted for 77.3% of the collected S. aureus isolates. USA100, traditionally healthcare associated (n=18/47, 38.3%), and USA300, traditionally community associated (n=12/47, 25.5%), were the dominant MRSA strains. Four (22.2%) of the USA100 MRSA isolates were recovered from patients with no prior healthcare exposure. Eleven (91.7%) of the USA300 isolates were recovered from patients with documented healthcare risk factors. MSSA isolates were polyclonal (n=13). Ninety-three percent of MSSA infections were of healthcare origin. Thirty-seven of 61 (60.6%) healthcare- and 11 of 14 (78.6%) community-associated strains were resistant to three or more antibiotic classes. Sixty-eight percent (n=51) of isolates harbored three of more resistance determinants (genes). The Panton-Valentine Leucocidin gene was detected in 11 (14.7%) of the study isolates. The majority (72.7%) of the strains were members of the USA300 MRSA clone.Conclusion: Clonal complexes CC5 and CC8 were the most frequent clones detected among both the MSSA and the MRSA keratitis isolates. USA100 and USA300 clones were the dominant MRSA genotypes. The USA300 MRSA clone has become a leading cause of healthcare-associated keratitis in South Florida. The USA100 MRSA clone has emerged as an increasing cause of community-associated corneal infections in our outpatient population. This shifting epidemiology coupled with the increasing prevalence of multidrug resistance among both MSSA and MRSA keratitis is a cause of concern. Keywords: MRSA, MSSA, DNA microarray, USA100, USA300, clones

Purpose To characterize the molecular, epidemiological, and resistance profiles of methicillin-resistant (MRSA) and methicillin-susceptible (MSSA) keratitis isolates. Patients and methods We used a combination of standard microbiological techniques and DNA microarray analysis to characterize the molecular and antibiotic resistance profiles of 75 Staphylococcus aureus keratitis isolates collected over an 11-year period (2006-2016). Results Two major USA clonal complexes (CC), CC5 (n=30, 40%) and CC8 (n=28, 37.3%), accounted for 77.3% of the collected S. aureus isolates. USA100, traditionally healthcare associated (n=18/47, 38.3%), and USA300, traditionally community associated (n=12/47, 25.5%), were the dominant MRSA strains. Four (22.2%) of the USA100 MRSA isolates were recovered from patients with no prior healthcare exposure. Eleven (91.7%) of the USA300 isolates were recovered from patients with documented healthcare risk factors. MSSA isolates were polyclonal (n=13). Ninety-three percent of MSSA infections were of healthcare origin. Thirty-seven of 61 (60.6%) healthcare- and 11 of 14 (78.6%) community-associated strains were resistant to three or more antibiotic classes. Sixty-eight percent (n=51) of isolates harbored three of more resistance determinants (genes). The Panton-Valentine Leucocidin gene was detected in 11 (14.7%) of the study isolates. The majority (72.7%) of the strains were members of the USA300 MRSA clone. Conclusion Clonal complexes CC5 and CC8 were the most frequent clones detected among both the MSSA and the MRSA keratitis isolates. USA100 and USA300 clones were the dominant MRSA genotypes. The USA300 MRSA clone has become a leading cause of healthcare-associated keratitis in South Florida. The USA100 MRSA clone has emerged as an increasing cause of community-associated corneal infections in our outpatient population. This shifting epidemiology coupled with the increasing prevalence of multidrug resistance among both MSSA and MRSA keratitis is a cause of concern.

To translate and validate a Spanish-language adaptation of the 5-Item Dry Eye Questionnaire for the Mexican population. Based on the MAPI Institute guidelines, the linguistic validation procedures consisted of four steps. Every step was reviewed by the committee. The translated validated questionnaire was applied to 25 Mexican subjects. The questionnaires were completed by the same subjects at three time points, 8 h apart on the same day and then 3 days later. Sensitivity and specificity of the DEQ-5 to predict DE signs was subsequently estimated in 200 patients see in the Asociacion para Evitar la Ceguera ophthalmology clinic. During the forward translation step analysis, the committee decided to change the severity scale, as the words “constantly” and “frequently” are synonymous in Spanish, so it was modified by changing “constantly” to “always” for better understanding. Overall, the intra-test intra-class correlation coefficient from tests administered on the same day was 0.9 (95% CI 0.77–0.95, p = 0.0005). The intra-test intra-class correlation coefficient from tests administered 3 days apart was 0.9 (95% CI 0.88–0.97, p = 0.0005). When applying the questionnaire to 200 patients seen in an eye clinic, we found a sensitivity of 76% and a specificity of 31% for a DEQ-5 score of ≥ 6, against 2 or more positive signs of dry eye. MAPI methodology proved to be a reliable strategy for the transcultural Dry Eye Questionnaire for translation from English to Spanish for the Mexican population.

IntroductionAlthough antibiotics are successful at achieving microbiological cure in infectious keratitis, outcomes are often poor due to corneal scarring. Ideal treatment of corneal ulcers would address both the infection and the inflammation. Adjunctive topical steroid treatment may improve outcomes by reducing inflammation. Corneal cross-linking (CXL) is a novel prospective therapy that may simultaneously reduce both inflammatory cells and bacterial pathogens. The purpose of this study is to determine differences in 6-month visual acuity between standard medical therapy with antibiotics versus antibiotics with adjunctive early topical steroid therapy versus antibiotic treatment plus CXL and early topical steroids.Methods and analysisThis international, randomised, sham and placebo-controlled, three-arm clinical trial randomises patients with smear positive bacterial ulcers in a 1:1:1 fashion to one of three treatment arms: (1) topical 0.5% moxifloxacin plus topical placebo plus sham CXL; (2) topical 0.5% moxifloxacin plus difluprednate 0.05% plus sham CXL; or (3) the CXL group: topical 0.5% moxifloxacin plus difluprednate 0.05% plus CXL.Ethics and disseminationWe anticipate that both adjunctive topical steroids and CXL will improved best spectacle corrected visual acuity and also reduce complications such as corneal perforation and the need for therapeutic penetrating keratoplasty. This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. Our results will be disseminated via ClinicalTrials.gov website, meetings and journal publications. Our data will also be available on reasonable request.Trial registration numberNCT04097730.

Purpose Chronic corneal endothelial cell (CEC) loss results in corneal edema and vision loss in conditions such as pseudophakic bullous keratopathy (PBK), Fuchs’ dystrophy, and corneal graft failure. Low CEC density has been associated with an elevation of intraocular pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α and interferon (INF)-γ. These cytokines are capable of triggering pyroptosis, a programmed cell death mechanism mediated by the inflammasome, prompting the activation of the pro-inflammatory cytokine interleukin (IL)-1β, the perpetuation of inflammation, and subsequent damage of corneal endothelial tissue. Therefore, the purpose of this study was to determine the deleterious contribution of the inflammasome and pyroptosis to CEC loss. Methods CECs from human donor corneas were treated ex vivo with TNF-α and IFN-γ for 48 h. Levels of caspase-1 and IL-1β were then assayed by ELISA, and the expression of caspase-1 and gasdermin-D (GSDM-D) were confirmed by immunofluorescence. Endothelial cell damage was analyzed by a lactate dehydrogenase (LDH) release assay, and oxidative stress was determined by measuring the levels of reactive oxygen species (ROS) in the culture media. Results Inflammasome activation and oxidative stress were elevated in CECs following exposure to TNF-α and IFN-γ, which resulted in cell death by pyroptosis as determined by LDH release which was inhibited by the caspase-1 inhibitor Ac-YVAD-cmk. Conclusion CEC death is induced by the pro-inflammatory cytokines TNF-α and IFN-γ, which contribute to inflammasome activation. Moreover, the inflammasome is a promising therapeutic target for the treatment of chronic CEC loss.

Limbal stem cell deficiency (LSCD) can be due to various causes and leads to corneal scarring and neovascularization as a common phenotypic endpoint. Patients require surgical intervention to manage pain/photophobia and restore vision. Patients should have a healthy donor limbus for an autograft, and the cause of LSCD should be resolved to avoid recurrence. Severe causes leading to LSCD might cause concomitant disease requiring further intervention (like keratoplasty, cataract extraction, pupilloplasty, etc.). Patients should be educated about the risks and benefits of the procedure, including alternatives.

Infectious keratitis is a sight-threatening microbial infection. The prevalence of antimicrobial resistance in cases of infectious keratitis has increased the demand for fortified compounded antimicrobial drops. Even with proper medical management, severe cases of infectious keratitis can further evolve into corneal perforation, requiring surgical intervention in the form of keratoplasty to control the infectious process. Due to the invasive nature of the procedure and the shortage of available donor tissue around the world, alternative treatments are needed for the management of progressive infectious keratitis. In ophthalmology, photodynamic therapy (PDT) has been used for numerous applications. PDT with Rose Bengal as a photosensitizer combined with green light optical irradiation (RB-PDAT) is a novel treatment with dual purpose: to arrest the infection from progressing and strengthen the collagen of the cornea. RB-PDAT may be considered as an adjunct therapy in severe cases of infectious keratitis to minimize the need for a therapeutic keratoplasty.