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Assess whether cross-linking the carrier donor cornea of the Boston Keratoprosthesis (BKPro) improves retention of the device in participants at high risk of keratolysis.Prospective, double-masked randomized clinical trial.In this multicenter study, sixty-eight adult participants who were scheduled for BKPro implantation were enrolled. Masked participants were randomized to receive either a cross-linked (CXL) or non-cross-linked (non-CXL) donor corneal carrier. Kaplan-Meier event-free survival was determined by the product-limit method and compared by the log-rank test to examine if survival curves were different between the CXL and non-CXL groups. The primary outcome of the study was time from surgery to BKPro removal. Secondary endpoint was twelve-month retention rate.Sixty-eight participants were enrolled and randomized 1:1 to each group. Average age at the time of surgery was 62 [24-89] years and 42 (62%) participants were male. Overall BKPro retention rate was 70% during a mean follow-up time of 93 (6 - 201) weeks. Twenty BKPros were removed, ten in the CXL group and ten in the non-CXL group, with 18 requiring removal because of sterile keratolysis. There was no difference in the time to removal between the groups during the study (P = 0.910). At twelve months, there was no significant difference in the retention rate in the CXL group (94%) versus the non-CXL group (82%, P = 0.150).In this prospective study, cross-linking of the carrier cornea prior to BKPro implantation did not reduce the incidence of sterile keratolysis or increase device retention among participants at high risk for retention failure.

To provide the initial confirmation of the c.1772CT (p.Ser591Phe) mutation in the transforming growth factor-Ophthalmologic examination of the proband was performed with slit lamp biomicroscopy. Saliva was collected as a source of DNA for screening all 17 exons ofSlit lamp examination of the 38-year-old proband revealed a clear cornea right eye and unilateral, discrete, and branching lattice lines in the anterior and mid-stroma of the central cornea left eye. Screening ofThe p.Ser591Phe mutation in

Congenital stromal corneal dystrophy (CSCD) is a rare congenital, dominantly inherited disorder characterized by diffuse stromal opacification associated with mutations in the decorin gene (DCN). As only 5 families with genetically confirmed CSCD have been reported, the identification of a novel pedigree provides the opportunity to better characterize the phenotype and genetic basis.An Armenian family with individuals in 4 consecutive generations demonstrated clinical features consistent with CSCD. Consented individuals underwent slit lamp examination, optical coherence tomography, and confocal microscopy. Genomic DNA was collected from saliva and all coding and adjacent intronic regions of DCN were sequenced. In silico analysis was performed for identified mutation(s). Excised corneal tissue underwent light, electron microscopic, and immunohistochemical evaluation.Affected individuals demonstrated bilateral, diffuse, panstromal corneal opacification. Three of the 6 individuals diagnosed with CSCD underwent genetic analysis; all demonstrated a novel heterozygous frameshift deletion in exon 8 of DCN (p.His317Thrfs*11), predicted to cause a 33 amino acid truncation and to be damaging and disease causing by SIFT and MutationTaster. Light and electron microscopic examination of an excised cornea demonstrated increased corneal thickness, stromal scarring, keratocyte loss, and an irregularity of lamellar collagen spacing and fibril formation. Immunofluorescent examination demonstrated increased DCN immunostaining, predominantly in the widened interlamellar spaces.We report only the sixth pedigree with genetically confirmed CSCD, associated with a novel DCN frameshift mutation. The clinical evaluation, multimodal imaging, and histopathologic assessment in this family with CSCD broaden our understanding of this rare corneal disease.

Background Concomitant corneal ectasia and posterior lamellar corneal opacification is rare, and the genetic relationship between these two conditions is unclear. We report the genetic and clinical characterization of this phenotype in three unrelated individuals. Materials and methods One previously reported affected individual and two unreported, unrelated, affected individuals were recruited for the study. Subjects and unaffected relatives underwent slit lamp examination, refraction, and multi-modal imaging. Saliva samples were obtained from two of the three affected individuals, from which DNA was extracted. Sanger sequencing was performed to identify mutations in genes associated with posterior amorphous corneal dystrophy (PACD), brittle cornea syndrome (BCS), and posterior polymorphous corneal dystrophy (PPCD), while copy number variation (CNV) analysis was used to identify CNV in the PACD locus. Results Affected individuals demonstrated bilateral corneal steepening, stromal thinning and lamellar posterior corneal opacification. Corneal topography and tomography revealed conical or globular corneal steepening and decreased thickness. Anterior segment optical coherence tomography demonstrated hyperreflectivity of the posterior stroma in each of the affected individuals. Genetic testing did not detect a heterozygous deletion involving the PACD locus on chromosome 12 or a pathogenic mutation in the genes associated with BCS or PPCD. Conclusions Corneal ectasia may be associated with posterior lamellar stromal opacification that appears consistent with PACD. However, genetic testing for PACD as well as BCS and PPCD in affected individuals fails to reveal pathogenic deletions or mutations, indicating that other genetic factors are involved.

Purpose The purpose of this study was to report a novel clinical entity characterized by bilateral calcium deposits in the flap interface after uncomplicated laser in situ keratomileusis (LASIK). Methods Slit-lamp examination, anterior segment optical coherence tomography imaging, and histopathologic analysis of an interface opacity were performed to characterize and identify the origin of the interface opacities. Results Two unrelated healthy young men who underwent LASIK in both eyes at 20 (case 1) and 44 (case 2) years of age were diagnosed with bilateral, white anterior stromal opacities 5 years after LASIK surgery. Slit-lamp examination and anterior segment optical coherence tomography imaging demonstrated that the opacities were located at the level of the LASIK interface in both eyes of both cases, with most of the opacities located at the temporal edge of the flap in each eye of case 2. An opacity from case 2 demonstrated birefringence using polarization microscopy and staining with Alizarin red, indicative of calcium deposition. The serum calcium level was borderline elevated in case 1 and within normal limits in case 2. Conclusions Intrastromal calcium deposition can occur after LASIK surgery, with the deposits resembling dystrophic deposits located in the LASIK flap interface in individuals with granular corneal dystrophy type 2. Because the etiology and management of calcific and dystrophic interface deposition after LASIK are distinct, it is important for clinicians to differentiate the 2 entities based on the examination, diagnostic imaging, and, if necessary, molecular genetic analysis.

Purpose The aim of this study was to report the results of screening peroxiredoxin 3 (PRDX3) and PDZ domain-containing protein 8 (PDZD8) in a previously unreported pedigree with punctiform and polychromatic pre-Descemet corneal dystrophy (PPPCD) to confirm that the PRDX3 mutation c.568G>C is the genetic basis of PPPCD. Methods Ophthalmologic examination of the proband and her affected father was performed with slit lamp biomicroscopy. Saliva was collected from the proband as a source of DNA, after which screening for PRDX3 and PDZD8 was performed. Results Slit lamp examination of the proband revealed polychromatic deposits diffusely distributed at the pre-Descemet level in both corneas and anterior subcapsular in the crystalline lens of both eyes. The proband's father also demonstrated diffuse pre-Descemetic polychromatic deposits in both eyes but no lenticular deposits. Screening of PRDX3 in the proband demonstrated the c.568G>C (p.Asp190His) variant previously associated with PPPCD and failed to identify any variants in PDZD8. Conclusions We report the initial confirmation of PRDX3 as the genetic basis of PPPCD in a previously unreported pedigree and expand the phenotype of PPPCD to include polychromatic lenticular deposits.

Most transforming growth factor beta-induced (Participants underwent slit-lamp examination and multimodal imaging. Polymerase chain reaction amplification and Sanger sequencing were performed on saliva-derived genomic DNA to screenA 56-year-old Thai woman reported a four-year history of decreased vision and intermittent eye irritation, suggestive of recurrent epithelial erosions, in both eyes. Slit-lamp exam revealed bilateral, irregular, limbal-sparing Bowman layer opacities, which were also noted on anterior segment optical coherence tomography. Phototherapeutic keratectomy was performed in the right eye, improving the best-corrected visual acuity from 20/50 to 20/30. Sequencing of theA novel

Meesmann epithelial corneal dystrophy (MECD) is a rare dominantly inherited disorder that is characterized by corneal epithelial microcysts and is associated with mutations in the keratin 3 (KRT3) and keratin 12 (KRT12) genes. In this study, we report a novel mutation in the KRT12 gene in a Vietnamese pedigree with MECD. Slit-lamp examination was performed on each of the 7 recruited members of a Vietnamese family to identify characteristic features of MECD. After informed consent was obtained from each individual, genomic DNA was isolated from saliva samples and screening of KRT3and KRT12 genes was performed by Sanger sequencing. The proband, a 31-year-old man, complained of a 1-year history of eye irritation and photophobia. Slit-lamp examination revealed intraepithelial microcysts involving only the corneal periphery in each eye with clear central corneas and no stromal or endothelial involvement. Three family members demonstrated similar intraepithelial microcysts, but with diffuse involvement, extended from limbus to limbus. Sanger sequencing of KRT3 (exon 7) and KRT12 (exons 1 and 6) in the proband revealed a novel heterozygous KRT12 variant (c.1273G>A [p.Glu425Lys]) that was present in the three affected family members but was absent in the three family members with clear corneas. This study is the first report of a Vietnamese family affected with MECD, associated with an atypical peripheral corneal epithelial phenotype in the proband and a novel mutation in KRT12.

The aim of this study was to describe the clinical presentation and multimodal imaging of a patient diagnosed with infectious crystalline keratitis (ICK) secondary to Mycobacterium chelonae .This is a case report of a patient with a crystalline corneal infiltrate imaged with anterior segment optical coherence tomography and in vivo scanning laser confocal microscopy. Bacterial, fungal, acanthamoeba, and acid-fast cultures were performed to identify the causal pathogen.Examination revealed a white stellate opacity in the midstroma underlying the scalloped border of an area of central corneal stromal thinning, consistent with a diagnosis of ICK. Anterior segment optical coherence tomography demonstrated a hyperreflective diamond-shaped opacity located at a depth of 334 μm, which demonstrated multiple stellate projections on in vivo scanning laser confocal microscopy. The acid-fast culture was positive for Mycobacterium chelonae .Although ICK is most commonly associated with Streptococcus species, it may be secondary to atypical bacteria including Mycobacterium species, underscoring the importance of diagnostic imaging and collecting corneal cultures to identify the pathogenic organism.

Purpose To compare the outcomes of Descemet membrane endothelial keratoplasty (DMEK) with those of Descemet's stripping endothelial keratoplasty (DSEK) in eyes with prior glaucoma surgery. Design Case-matched retrospective comparative case series. Methods Setting/study population: 46 DMEK procedures were matched with 46 DSEK procedures at a single institution. Observation procedures: cases were matched based on preoperative visual acuity, lens status, and surgical indication. Main outcome measurements: the outcome measurements included visual acuity improvement, primary and secondary graft failure, endothelial rejection, intraocular pressure (IOP) elevation, and the need for additional glaucoma intervention. Results Best-corrected visual acuity (BCVA) improved by −0.89 logMAR in the DMEK group and −0.62 logMAR in the DSEK group (P = 0.005) at 1 year follow-up. Visual acuity was significantly better in the DMEK group at postoperative months 1, 3, and 12 and at last follow-up. The percentage of patients achieving 20/40 or better best-corrected visual acuity was higher in the DMEK group at all time points, notably 47% in the DMEK group versus 15% in the DSEK group at 1 year (P = 0.002). Secondary graft failure was lower in the DMEK group (DMEK 0% vs. DSEK 17%; P = 0.006). Primary graft failure rates and rebubling rates were similar. There were no differences in the rates of postoperative IOP elevation or in the need for additional glaucoma intervention. Conclusions In complex eyes with prior glaucoma surgery, DMEK offers faster visual recovery, better final visual acuity, and a lower rate of secondary graft failure compared to DSEK during the first postoperative year and beyond.

PURPOSE: To examine the association of donor, recipient, and operative factors on graft dislocation after Descemet stripping automated endothelial keratoplasty (DSAEK) in the Cornea Preservation Time Study (CPTS) as well as the effects of graft dislocation and elevated IOP on graft success and endothelial cell density (ECD) 3 years postoperatively. DESIGN: Cohort study within a multi-center, double-masked, randomized clinical trial. METHODS: 1,090 individuals (1,330 study eyes), median age 70 years, undergoing DSAEK for Fuchs endothelial corneal dystrophy (94% of eyes) or pseudophakic or aphakic corneal edema (6% of eyes). Recipient eyes receiving donor corneal tissue randomized by preservation time (PT) of 0-7 days (N=675) or 8-14 days (N=655) were monitored for early or late graft failure through 3 years. Donor, recipient, operative, and postoperative parameters were recorded including graft dislocation (GD), partial detachment, and pre- and post-operative IOP. Pre- and postoperative central donor ECD were determined by a central image analysis reading center. Proportional hazards, mixed effects, and logistic regression models estimated risk ratios and {99% confidence intervals}. RESULTS: Three independent predictive factors for GD were identified: a history of donor diabetes (odds ratio {OR}: 2.29 {1.30, 4.02}), increased pre-lamellar dissection central corneal thickness (OR: 1.13 {1.01, 1.27} per 25μ increase), and operative complications (OR: 2.97 {1.24, 7.11}). Among 104 (8%) eyes with GD, 30 (28.9%) developed primary donor or early failure and 5 (4.8%) developed late failure vs. 15 (1.2%; p

Recurrent corneal erosion syndrome (RCES) is a disorder characterised by a dysfunctional epithelial ecosystem. It often begins after trauma, or in the setting of epithelial basement membrane degeneration or dystrophy. Historically, RCES has been understood as a structural derangement of the anterior corneal architecture. More recently, studies have demonstrated the important role of neuropeptides in corneal homoeostasis. Thus, RCES may also be understood as a disorder of corneal epithelial cell biology. Management of RCES can be challenging, but newer therapies have demonstrated improved efficacy for this condition. This review examines the aetiology and pathogenesis of RCES, and provides an update on current and emerging treatment modalities for the management of this disorder.

PURPOSE To identify the incidence, risk factors, and outcomes of infectious keratitis after Boston type 1 keratoprosthesis (kpro) implantation. METHODS Retrospective case series of kpro procedures at the Stein Eye Institute and the Centre Hospitalier de l'Universite de Montreal between May 1, 2004, and December 31, 2018. Data were collected regarding ocular history, operative details, postoperative management, microbiologic profile, treatment, and outcomes. Log-rank test and Cox proportional hazard ratio (HR) were used to evaluate for an association between risk factors and outcomes. RESULTS A total of 349 kpro procedures were performed in 295 eyes of 268 patients. Fifty-seven cases of presumed infectious keratitis were identified after 53 procedures (15.2%) in 50 eyes (16.9%) of 49 patients (18.3%). The incidences of culture-positive bacterial and fungal keratitis were 0.014 and 0.004 per eye-year, respectively. Persistent corneal epithelial defect formation (P < 0.001) and cicatricial disease (HR: 1.98, 95% confidence interval, 1.02-3.83) were associated with a significantly higher incidence of infectious keratitis. For the 53 cases with a known outcome, medical therapy achieved resolution of infection in 34 cases (64.2%), whereas kpro explantation was required in 19 cases (35.8%). Infectious keratitis was associated with an increased risk for kpro explantation (HR: 3.09, 95% confidence interval, 1.92-4.79). CONCLUSIONS Infectious keratitis develops in approximately 17% of eyes after kpro implantation, with a higher rate of culture-positive bacterial than fungal keratitis. The observed rate of microbial keratitis suggests the need for additional topical antimicrobial prophylaxis in eyes at higher risk, such as those with preexisting cicatricial disease or postoperative persistent corneal epithelial defect formation.

AIM: To report the etiologies, risk factors, treatments, and outcomes of infectious keratitis (IK) at a major Vietnamese eye hospital. METHODS: This is a retrospective review of all cases of IK at Vietnam National Eye Hospital (VNEH) in Hanoi, Vietnam. Medical histories, demographics, clinical features, microbiological results, and treatment outcomes were reviewed. RESULTS: IK was diagnosed in 1974 eyes of 1952 patients, with ocular trauma being the greatest risk factor for IK (34.2%), frequently resulting from an agriculture-related injury (53.3%). The mean duration between symptom onset and presentation to VNEH was 19.3±14.4d, and 98.7% of patients had been treated with topical antibiotic and/or antifungal agents prior to evaluation at VNEH. Based on smear results of 1706 samples, the most common organisms identified were bacteria (n=1107, 64.9%) and fungi (n=1092, 64.0%), with identification of both bacteria and fungi in 614 (36.0%) eyes. Fifty-five of 374 bacterial cultures (14.7%) and 426 of 838 fungal cultures (50.8%) were positive, with the most commonly cultured pathogens being Pseudomonas aeruginosa, Streptococcus pneumonia, Fusarium spp., and Aspergillus spp. Corneal perforation and descemetocele developed in 391 (19.8%) and 93 (4.7%) eyes, respectively. Medical treatment was successful in resolving IK in 50.4% eyes, while 337 (17.1%) eyes underwent penetrating or anterior lamellar keratoplasty. Evisceration was performed in 7.1% of eyes, most commonly in the setting of fungal keratitis. CONCLUSION: Ocular trauma is a major risk factor for IK in Vietnam, which is diagnosed in almost 400 patients each year at VNEH. Given this, and as approximately one quarter of the eyes that develop IK require corneal transplantation or evisceration, greater emphasis should be placed on the development of prevention and treatment programs for IK in Vietnam.

Purpose To report complications of cosmetic artificial iris implantation and explantation outcomes. Design Retrospective case series. Methods Medical records of 12 patients (24 eyes) who presented to us after being implanted with cosmetic artificial irises elsewhere were reviewed. Data collected included baseline demographics, presenting symptoms, examination findings, and management outcomes. Results Eight eyes had NewColorIris implants and 16 had BrightOcular implants. The mean interval from cosmetic iris implantation to presentation was 61.7 ± 60.0 months. The mean follow-up after explantation was 35.5 ± 38.1 months. Complications at presentation included iris abnormalities (11 eyes, 45.8%), elevated intraocular pressure (8 eyes, 33.3%), corneal edema (6 eyes, 25%), intraocular inflammation (5 eyes, 20.8%), and cataract (4 eyes, 16.7%). Surgical interventions included cosmetic iris removal (19 eyes, 79.2%), cataract extraction (7 eyes, 29.2%), corneal transplantation (7 eyes, 29.2%), and glaucoma surgery (4 eyes, 16.7%). Complications at the last follow-up examination included native iris defects (11 eyes, 45.8%), persistent glaucoma (7 eyes, 29.2%), cataract (5 eyes, 20.8%), corneal edema (4 eyes, 16.7%), and intraocular inflammation (2 eyes, 8.3%). The mean logarithm of the minimum angle of resolution was 0.56 ± 0.47 at presentation and 0.78 ± 0.88 at the last examination (P = .30). The mean intraocular pressure was 22.7 ± 15.8 mm Hg at presentation and 13.4 ± 6.99 mm Hg at the last examination (P = .02). Conclusion Cosmetic iris implantation was associated with serious complications at the time of presentation, and adverse sequelae persisted for years after explantation.

Author(s): Bonnet, Clemence; Vazirnia, Parsia; Deng, Sophie X; Aldave, Anthony J; Miller, Kevin M | Abstract: PurposeTo assess safety and efficacy outcomes of sutured custom silicone artificial iris and intraocular lens implantation combined with penetrating keratoplasty (triple procedure).MethodsProspective consecutive surgical case series of patients who underwent the triple procedure between 2010 and 2019 at Stein Eye Institute, UCLA, followed up for 1 year minimum. Safety outcomes were changes from preoperative to last follow-up in corrected distance visual acuity (CDVA), endothelial cell count, intraocular pressure (IOP), and postoperative complications. Efficacy outcomes included changes in subjective glare (none to severe), cosmetic appearance (worse to very much improved), and visual function as assessed by the Visual Function Questionnaire-25 at 1-year follow-up.ResultsAmong 82 eyes implanted with an artificial iris, 14 eyes (17.1%) underwent the triple procedure. The median follow-up was 18.1 months (range 12.0-54.9 months). The median CDVA improved from 2.0 log of minimum angle of resolution (logMAR) (range 0.9-2.3 logMAR) to 0.7 logMAR (range 0.2-2.6 logMAR) (P = 0.02). Average endothelial cell count decreased 57.6% (P l 0.01). Six eyes (42.9%) experienced IOP elevations, 13 eyes (92.3%) developed iritis, and 11 eyes (78.6%) underwent secondary surgery. Graft rejection or secondary graft failure occurred in 7 eyes each (50.0%). Cosmesis improved in 12 eyes (85.7%; P l 0.01). The Visual Function Questionnaire-25 score improved from 72 to 77 (P l 0.01). Glare symptoms did not change significantly.ConclusionsThe triple procedure was effective at improving CDVA, cosmesis, and quality of life; however, it was associated with frequent postoperative complications, of which iritis, IOP elevation, and secondary graft failure were the most common.

To determine incidence, risks factors for, and outcomes of idiopathic vitritis (IV) after Boston type 1 keratoprosthesis (KPro) implantation.Retrospective, consecutive case series. Risk factors were analyzed between IV group and No IV group.IV occurred in 32/350 procedures (9.1%), for an average incidence of 0.02 cases per procedure-year. Presumed infectious keratitis was the only risk factor identified (HR = 7.65) Corneal necrosis and retinal detachment occurred significantly more frequently in IV group (allIV is associated with infectious keratitis, indicating that the vitritis may not be a sterile process. The increased incidence of subsequent complications leads to significantly decreased visual acuity and KPro retention in affected eyes.

Background Keratitis-ichthyosis-deafness (KID) syndrome is characterized by a congenital triad of keratitis, ichthyosis, and deafness, and is most commonly associated with mutations in the gap junction protein beta 2 gene (GJB2) on chromosome 13q11-q12. Methods Multimodal anterior segment imaging and genetic testing were used to supplement clinical examination findings in the diagnosis and management of a 12-year-old boy with suspected KID syndrome. Results The patient presented with hearing loss, ichthyosis of the face and extremities, and corneal scarring and keratinization. The corneal limbal stem cell population was found to be normal on in vivo confocal microscopy, whereas the basal epithelium of the cornea demonstrated scarring and areas of cellular loss. Screening of GJB2 revealed a presumed pathogenic heterozygous missense mutation, c.148G>A, confirming the diagnosis of KID syndrome. Conclusions Multimodal imaging including in vivo confocal microscopy suggests that dysfunctional corneal basal epithelium maturation might contribute to the pathophysiology of keratopathy in KID syndrome.

Purpose To describe the causes and prevalence of moderate-to-severe visual impairment (MSVI) and blindness from corneal diseases, as well as corneal transplantation across Asia. Methods A meta-analysis of the published literature to identify population-based surveys conducted from 2008 to 2019 in 22 Asian countries regarding the prevalence and causes of MSVI and blindness from corneal disease, and a review of national corneal transplant data and eye bank statistics. Results A total of 5307 records were screened to identify 57 reports that were used to estimate a prevalence of MSVI and blindness caused by corneal diseases in Asia of 0.38% (95% confidence interval, 0.29%-0.48%). The most frequent corneal diseases were infectious keratitis, trauma, and pseudophakic bullous keratopathy. As expected, these represented the most common indications for corneal transplantation, although the percentages in each country differed based on the level of economic development, with pseudophakic bullous keratopathy being the most common indication in countries with higher gross national income per capita. Despite this, endothelial keratoplasty is not the most commonly performed form of corneal transplantation in any Asian country and represents only a small percentage of keratoplasty procedures performed in most countries. Conclusions The prevalence of MSVI and blindness from corneal disease in Asia is approximately 0.4%, with a nearly 20-fold difference in the national prevalence across the region. The indications for keratoplasty, reflective of the causes of corneal dysfunction, also vary, more so according to the gross national income than to geographic location, and only a few Asian countries have rates of corneal transplantation above international means.

Purpose To investigate the presence of pre-Descemet corneal dystrophy (PDCD) in association with X-linked ichthyosis (XLI) in an 11-year-old boy using multimodal imaging and genetic analysis. Methods Corneal opacities were examined and imaged with slit-lamp biomicroscopy, anterior segment optical coherence tomography, noncontact specular microscopy, and in vivo confocal microscopy. Cytogenomic array analysis was performed using genomic DNA isolated from the patient. Results Corneal opacities characteristic of PDCD located in the posterior corneal stroma just anterior to Descemet membrane were identified by slit-lamp biomicroscopy. A pre-Descemet hyper-reflective line, consistent with these opacities, was seen with anterior segment optical coherence tomography. Scheimpflug tomography revealed a bimodal peak light scattering. In vivo confocal microscopy findings were unremarkable. Copy number analysis identified a 4389 kbp hemizygous deletion on the X chromosome (chr. X: 6,540,898-8,167,604), resulting in the deletion of 4 genes, including the known locus of XLI, the STS gene. Conclusions This report demonstrates that PDCD-associated XLI may present in children and that the diagnosis may be confirmed through multimodal imaging in conjunction with genetic analysis.

The advent of cell culture-based methods for the establishment and expansion of human corneal endothelial cells (CEnC) has provided a source of transplantable corneal endothelium, with a significant potential to challenge the one donor-one recipient paradigm. However, concerns over cell identity remain, and a comprehensive characterization of the cultured CEnC across serial passages has not been performed. To this end, we compared two established CEnC culture methods by assessing the transcriptomic changes that occur during in vitro expansion. In confluent monolayers, low mitogenic culture conditions preserved corneal endothelial cell state identity better than culture in high mitogenic conditions. Expansion by continuous passaging induced replicative cell senescence. Transcriptomic analysis of the senescent phenotype identified a cell senescence signature distinct for CEnC. We identified activation of both classic and new cell signaling pathways that may be targeted to prevent senescence, a significant barrier to realizing the potential clinical utility of in vitro expansion.

Infectious keratitis after lamellar keratoplasty is a potentially devastating complication that may severely limit the visual and anatomical outcomes. The deep-seated location of the infiltrates, sequestration of the pathogenic microorganisms and limited penetration of the currently available antimicrobial agents often results in delayed diagnosis that may jeopardize the management in these cases. Fungal keratitis is more common as compared with bacterial or viral keratitis and classically presents as white interface infiltrates that may not be associated with significant inflammation. Confocal microscopy may help to establish a rapid diagnosis in such cases, and anterior segment optical coherence tomography may be used to determine the extent of infection and monitor its progression. Conservative measures such as topical antimicrobials and interface irrigation with antimicrobial agents may be done. Surgical intervention in the form of partial excision/removal of the graft in endothelial keratoplasty or a full-thickness keratoplasty is often required for the effective management of deep-seated infections. Timely diagnosis and intervention may result in complete resolution of infection in both anterior lamellar and endothelial keratoplasty. Infections after anterior lamellar keratoplasty have a fair prognosis, and a clear graft with functional visual acuity may be achieved in most cases. By contrast, infections after endothelial keratoplasty have a guarded prognosis, and the presence of concomitant endophthalmitis may further complicate the graft survival and visual outcomes.

PurposeTo elucidate the molecular events in solute carrier family 4 member 11 (SLC4A11)-deficient corneal endothelium that lead to the endothelial dysfunction that characterizes the dystrophies associated withSLC4A11mutations, congenital hereditary endothelial dystrophy (CHED) and Fuchs endothelial corneal dystrophy 4.MethodsComparative transcriptomic analysis (CTA) was performed in primary human corneal endothelial cells (pHCEnC) and murine corneal endothelial cells (MCEnC) with normal and reduced levels of SLC4A11 (SLC4A11KD pHCEnC) and Slc4a11 (Slc4a11−/−MCEnC), respectively. Validation of differentially expressed genes was performed using immunofluorescence staining of CHED corneal endothelium, as well as western blot and quantitative PCR analysis ofSLC4A11KD pHCEnC andSlc4a11−/−MCEnC. Functional analyses were performed to investigate potential functional changes associated with the observed transcriptomic alterations.ResultsCTA revealed inhibition of cell metabolism and ion transport function as well as mitochondrial dysfunction, leading to reduced adenosine triphosphate (ATP) production, inSLC4A11KD pHCEnC andSlc4a11−/−MCEnC. Co-localization of SNARE protein STX17 with mitochondria marker COX4 was observed in CHED corneal endothelium, as was activation of AMPK–p53/ULK1 in bothSLC4A11KD pHCEnC andSlc4a11−/−MCEnC, providing additional evidence of mitochondrial dysfunction and mitophagy. Reduced Na+-dependent HCO3−transport activity and altered NH4Cl-induced membrane potential changes were observed inSlc4a11−/−MCEnC.ConclusionsReduced steady-state ATP levels and subsequent activation of the AMPK–p53 pathway provide a link between the metabolic functional deficit and transcriptome alterations, as well as evidence of insufficient ATP to maintain the Na+/K+-ATPase corneal endothelial pump as the cause of the edema that characterizesSLC4A11-associated corneal endothelial dystrophies.

Purpose: Macular Corneal Dystrophy (MCD, MIM #217800) is a category 1 corneal stromal dystrophy as per the current IC3D classification. While characterized by macular stromal deposits, we report a case of MCD type II with isolated bilateral peripheral Decemet membrane opacities, describing the clinical features and results of screening the CHST6 gene and serum sulfated keratan sulfate levels. Observations: A 68-year-old man with an unremarkable past medical and family history presented with bilateral progressive decrease in vision. Ocular exam revealed bilateral clear corneas with the exception of peripheral, round, gray-white discrete deposits at the level of Descemet membrane and decreased central corneal thickness in both eyes. The morphology of the corneal deposits, decreased corneal thickness and the absence of a family history were consistent with MCD, prompting screening of the CHST6 gene. Sanger sequencing followed by allele specific cloning revealed compound heterozygous CHST6 mutations in trans configuration: c.-26C > A, which created a new upstream open reading frame (uORF’), predicted to attenuate translation efficiency of the downstream main ORF; and c.803A > G (p.(Tyr268Cys)), previously associated with MCD. Serum keratan sulfate was reduced but detectable, consistent with the diagnosis of macular corneal dystrophy type II. Conclusions: Although macular corneal dystrophy is classified as a corneal stromal dystrophy with endothelial involvement, we report a case of MCD with dystrophic deposits confined to the peripheral Descemet membrane, indicating that MCD may be associated with isolated endothelial involvement. Keywords: Corneal dystrophy, Macular corneal dystrophy, Corneal endothelial disease

Purpose To determine the prevalence of the transforming growth factor (TGF) β–induced gene corneal dystrophies in refractive surgery candidates in China. Setting Five hospitals in China. Design Prospective case series. Method Refractive surgical candidates from 5 preselected eye hospitals/centers in China were recruited after providing informed consent. All patients had slitlamp biomicroscopy and collection of a buccal swab as a source of DNA for screening of the TGF β–induced gene for the 5 most common mutations associated with Reis-Buckler corneal dystrophy, Thiel-Behnke corneal dystrophy, granular corneal dystrophy type 1, granular corneal dystrophy type 2, and lattice corneal dystrophy type 1. Results Of the 2068 refractive surgery candidates analyzed, 4 had corneal opacities in both eyes on slitlamp examination. Screening for the TGF β–induced gene found the heterozygous p.R124H mutation associated with granular corneal dystrophy type 2 in each of the 4 individuals with corneal opacities as well as in a fifth individual who did not have any corneal opacities, for a prevalence of 0.24%. Exacerbation of dystrophic corneal deposition developed after laser refractive surgery in 2 individuals who did not have preoperative TGF β–induced gene screening. Conclusions The prevalence of the TGF β–induced gene corneal dystrophies in Chinese refractive surgery candidates was estimated to be approximately 0.24%. Genetic testing is recommended to identify and exclude from candidacy all individuals with a TGF β–induced gene dystrophy before elective keratorefractive surgery to avoid causing accelerated postoperative dystrophic deposition.

Purpose To report the long-term outcomes of the Boston type I keratoprosthesis (KPro). Methods Data were collected regarding preoperative characteristics, surgical procedure(s) performed, and postoperative outcomes of patients who underwent KPro implantation from May 1, 2004, to May 1, 2011, and were followed for 5 years after surgery. Results Seventy-four KPro procedures were performed in 58 eyes (55 patients), with more than 1 KPro implanted in 10 eyes. The mean follow-up duration was 82.8 ± 20.5 months (range 57-145 months), and the most common indication for keratoprosthesis implantation was corneal transplant failure (50%). Preoperative corrected distance visual acuity (CDVA) was ≥20/200 in 5%; between 1 and 8 years after surgery, the percentage of eyes with CDVA ≥20/200 varied between 57% (4 years) and 82% (8 years). Nineteen (25.7%) KPros implanted were removed (retention failure rate 0.047/eye-year), although a KPro was retained at final follow-up in 55 eyes (94.8%). The most common postoperative complication was retroprosthetic membrane formation in 51.7% of eyes. The incidence of each postoperative complication decreased significantly over the first 10 years after surgery. Conclusions The KPro provides significant visual improvement in most eyes, with more than 50% regaining and maintaining 20/200 CDVA each year through 8 years after surgery. The incidence of each postoperative complication decreases significantly over the first 10 years after surgery. Although almost one-quarter of implanted keratoprostheses were removed, over 90% of eyes reaching 5 years of follow-up retain a keratoprosthesis at final follow-up.

The structure of the cornea is vital to its transparency, and dystrophies that disrupt corneal organization are highly heritable. To understand the genetic aetiology of Fuchs endothelial corneal dystrophy (FECD), the most prevalent corneal disorder requiring transplantation, we conducted a genome-wide association study (GWAS) on 1,404 FECD cases and 2,564 controls of European ancestry, followed by replication and meta-analysis, for a total of 2,075 cases and 3,342 controls. We identify three novel loci meeting genome-wide significance (P, Fuchs endothelial corneal dystrophy (FECD) is one of the most common reasons for corneal transplantation, and is known to cluster in families. Here, the authors discover new genetic loci associated with FECD with sex-specific effects and implications for disease mechanism.

Purpose To investigate the molecular basis of posterior polymorphous corneal dystrophy (PPCD) by examining the PPCD transcriptome and the effect of decreased ZEB1 expression on corneal endothelial cell (CEnC) gene expression. Methods Next-generation RNA sequencing (RNA-seq) analyses of corneal endothelium from two PPCD-affected individuals (one with PPCD3 and one of unknown genetic cause) compared with two age-matched controls, and primary human CEnC (pHCEnC) transfected with siRNA-mediated ZEB1 knockdown. The expression of selected differentially expressed genes was validated by quantitative polymerase chain reaction (qPCR) and/or assessed by in situ hybridization in the corneal endothelium of four independent cases of PPCD (one with PPCD3 and three of unknown genetic cause). Results Expression of 16% and 46% of the 104 protein-coding genes specific to ex vivo corneal endothelium was lost in the endothelium of two individuals with PPCD. Thirty-two genes associated with ZEB1 and 3 genes (BMP4, CCND1, ZEB1) associated with OVOL2 were differentially expressed in the same direction in both individuals with PPCD. Immunohistochemistry staining and RNA-seq analyses demonstrated variable expression of type IV collagens in PPCD corneas. Decreasing ZEB1 expression in pHCEnC altered expression of 711 protein-coding genes, many of which are associated with canonical pathways regulating various cellular processes. Conclusions Identification of the altered transcriptome in PPCD and in a cell-based model of PPCD provided insight into the molecular alterations characterizing PPCD. Further study of the differentially expressed genes associated with ZEB1 and OVOL2 is expected to identify candidate genes for individuals with PPCD and without a ZEB1 or OVOL2 mutation.

Purpose To evaluate the safety of concurrent Boston type I keratoprosthesis (KPro) and glaucoma drainage device (GDD) implantation. Design Retrospective comparative study of a consecutive cohort of patients. Subjects Patients who underwent KPro implantation by a single surgeon (A.J.A.) with or without 1 concurrent Ahmed GDD (New World Medical, Inc., Rancho Cucamonga, CA) implantation between January 1, 2005, and January 31, 2015, were included. Patients with fewer than 3 months of follow-up or a history of previous KPro implantation were excluded. Methods Preoperative, operative, and postoperative data were collected for each procedure. All comparisons were made between KPro procedures performed with or without concurrent GDD implantation. The Fisher exact test (2-tailed) was used to compare proportions, Student t test and Wilcoxon rank-sum test were used to compare means, and the log-rank test was used to compare time-to-outcome events. Main Outcome Measures The primary outcome was frequency of the composite variable, that is, any serious vision-threatening postoperative complication, which included sterile vitreitis, endophthalmitis, hypotony maculopathy, suprachoroidal hemorrhage, retinal detachment, stromal necrosis, and infectious keratitis. Secondary outcomes included intraocular pressure control, worsening of visual acuity, cystoid macular edema, retroprosthetic membrane formation, persistent epithelial defect formation, GDD exposure, and KPro removal. Results One hundred thirty-seven KPro procedures were performed in 129 patients: 91 (66.4%) KPro alone and 46 (33.6%) KPro plus GDD. There were no statistically significant differences between the 2 groups in terms of the incidence of vision-threatening postoperative complications. None of the 46 GDDs placed at the same time as the KPro became exposed during an average follow-up of 44 months. Conclusions Compared with KPro alone, GDD placement combined with KPro was not associated with increased postoperative complications.