Descemet Stripping Endothelial Keratoplasty in Patients With a Custom Foldable Silicone Artificial Iris: Safety and Efficacy Outcomes.

PURPOSE: To assess outcomes of Descemet stripping endothelial keratoplasty (DSEK) in eyes with custom artificial iris (CAI) implantation. METHODS: This is a retrospective, interventional, consecutive, surgical case series of patients who underwent DSEK after CAI implantation between 2010 and 2021 at 2 referral centers. Primary safety measures were loss of corrected distance visual acuity (CDVA), increase in intraocular pressure (IOP), development or progression of glaucoma, and intraoperative and postoperative complications. Efficacy measures were graft survival at year 1 and improvement in cosmesis at postoperative month 3. In general, measures were compared between baseline and postoperative year 1 while any complication was reported for the full follow-up period. RESULTS: Thirty-nine eyes of 39 patients were identified. 64.1% of eyes had acquired aniridia from trauma. The mean follow-up interval was 27.7 months (range 12.2-117.4). Median CDVA improved from logMAR 1.0 to 0.7 at year 1 (P = 0.0047). At the final follow-up, permanent loss of CDVA occurred in 25.6% of eyes, of which 90% was due to glaucoma. The most common postoperative complication was IOP elevation (66.7% of eyes). Graft survival at postoperative year 1 was 82.0% (95% confidence interval, 66.3-91.4). Secondary graft failure occurred in 28.2% of eyes at a mean duration of 39.7 months (SD 27.9 months) after DSEK. Cosmesis improved among 87.2% of eyes at postoperative month 3. CONCLUSIONS: DSEK is an effective procedure for addressing corneal edema in eyes with a CAI, but a majority develop elevated IOP and graft survival is shorter than in eyes without a CAI.

Investigation of the functional impact of CHED- and FECD4-associated SLC4A11 mutations in human corneal endothelial cells.

Mutations in the solute linked carrier family 4 member 11 (SLC4A11) gene are associated with congenital hereditary endothelial dystrophy (CHED) and Fuchs corneal endothelial dystrophy type 4 (FECD4), both characterized by corneal endothelial cell (CEnC) dysfunction and/or cell loss leading to corneal edema and visual impairment. In this study, we characterize the impact of CHED-/FECD4-associated SLC4A11 mutations on CEnC function and SLC4A11 protein localization by generating and comparing human CEnC (hCEnC) lines expressing wild type SLC4A11 (SLC4A11WT) or mutant SLC4A11 harboring CHED-/FECD4-associated SLC4A11 mutations (SLC4A11MU). SLC4A11WT and SLC4A11MU hCEnC lines were generated to express either SLC4A11 variant 2 (V2WT and V2MU) or variant 3 (V3WT and V3MU), the two major variants expressed in ex vivo hCEnC. Functional assays were performed to assess cell barrier, proliferation, viability, migration, and NH3-induced membrane conductance. We demonstrate SLC4A11-/- and SLC4A11MU hCEnC lines exhibited increased migration rates, altered proliferation and decreased cell viability compared to SLC4A11WT hCEnC. Additionally, SLC4A11-/- hCEnC demonstrated decreased cell-substrate adhesion and membrane capacitances compared to SLC4A11WT hCEnC. Induction with 10mM NH4Cl led SLC4A11WT hCEnC to depolarize; conversely, SLC4A11-/- hCEnC hyperpolarized and the majority of SLC4A11MU hCEnC either hyperpolarized or had minimal membrane potential changes following NH4Cl induction. Immunostaining of primary hCEnC and SLC4A11WT hCEnC lines for SLC4A11 demonstrated predominately plasma membrane staining with poor or partial colocalization with mitochondrial marker COX4 within a subset of punctate subcellular structures. Overall, our findings suggest CHED-associated SLC4A11 mutations likely lead to hCEnC dysfunction, and ultimately CHED, by interfering with cell migration, proliferation, viability, membrane conductance, barrier function, and/or cell surface localization of the SLC4A11 protein in hCEnC. Additionally, based on their similar subcellular localization and exhibiting similar cell functional profiles, protein isoforms encoded by SLC4A11 variant 2 and variant 3 likely have highly overlapping functional roles in hCEnC.

Lisch Epithelial Corneal Dystrophy Is Caused by Heterozygous Loss-of-Function Variants in MCOLN1.

PURPOSE: To report the genetic etiology of Lisch epithelial corneal dystrophy (LECD). DESIGN: Multicenter cohort study. METHODS: A discovery cohort of 27 individuals with LECD from 17 families, including 7 affected members from the original LECD family, 6 patients from 2 new families and 14 simplex cases, was recruited. A cohort of 6 individuals carrying a pathogenic MCOLN1 (mucolipin 1) variant was reviewed for signs of LECD. Next-generation sequencing or targeted Sanger sequencing were used in all patients to identify pathogenic or likely pathogenic variants and penetrance of variants. RESULTS: Nine rare heterozygous MCOLN1 variants were identified in 23 of 27 affected individuals from 13 families. The truncating nature of 7 variants and functional testing of 1 missense variant indicated that they result in MCOLN1 haploinsufficiency. Importantly, in the homozygous and compound-heterozygous state, 4 of 9 LECD-associated variants cause the rare lysosomal storage disorder mucolipidosis IV (MLIV). Autosomal recessive MLIV is a systemic disease and comprises neurodegeneration as well as corneal opacity of infantile-onset with epithelial autofluorescent lysosomal inclusions. However, the 6 parents of 3 patients with MLIV confirmed to carry pathogenic MCOLN1 variants did not have the LECD phenotype, suggesting MCOLN1 haploinsufficiency may be associated with reduced penetrance and variable expressivity. CONCLUSIONS: MCOLN1 haploinsufficiency is the major cause of LECD. Based on the overlapping clinical features of corneal epithelial cells with autofluorescent inclusions reported in both LECD and MLIV, it is concluded that some carriers of MCOLN1 haploinsufficiency-causing variants present with LECD.

Keratitis Fugax Hereditaria Associated With a Novel NLRP3 Mutation in a Non-Finnish Patient.

PURPOSE: The aim of this study was to report a novel heterozygous variant c.1712G>T (p.Gly571Val) in the nucleotide-binding domain, leucine-rich repeat family, pyrin domain-containing 3 gene ( NLRP3 ) in a previously unreported non-Finnish individual with keratitis fugax hereditaria (KFH). METHODS: Ophthalmologic examination of the proband was performed with slit-lamp biomicroscopy and anterior segment optical coherence tomography. Saliva was collected as a source of DNA, after which targeted exome sequencing of candidate genes was performed using a commercially available panel. Identified presumed pathogenic variants were confirmed by Sanger sequencing. RESULTS: Slit-lamp examination of the 52-year-old female proband revealed peripheral arcus-like degeneration and bilateral central corneal opacification, observed on anterior segment optical coherence tomography to involve the anterior half of the corneal stroma. Examination of the proband's parents revealed clear corneas in each eye. Genetic testing of the proband identified the presence of a novel heterozygous NLRP3 missense mutation (c.1712G>T, p.Gly571Val), which was confirmed by Sanger sequencing. This mutation was absent in the proband's parents. CONCLUSIONS: Although KFH has been reported only in individuals of Finnish descent and only in association with a missense mutation in exon 1 of NLRP3 , we report an individual of non-Finnish descent with KFH associated with a novel heterozygous variant in exon 2 of NLRP3 . Thus, ophthalmologists should be aware of the ethnic and genetic heterogeneity associated with KFH.

Chronic hypotony and uveitis managed with pars plana vitrectomy, silicone oil tamponade, and permanent keratoprosthesis.

PURPOSE: We report a case of silicone oil placement after Boston Type 1 keratoprosthesis implantation for improvement and maintenance of intraocular pressure in a patient with chronic hypotony secondary to chronic uveitis. METHODS: Observational case report. RESULTS: A 54-year-old female with a history of bilateral chronic panuveitis and subsequent hypotony presented with progressive corneal decompensation and band keratopathy in her better-seeing left eye. Her CDVA in her left eye declined from count fingers at 3' to hand motion. In an effort to clear the visual axis and stabilize intraocular pressure, implantation of a Boston Type 1 Keratoprosthesis combined with pars plana vitrectomy and silicone oil injection was performed. Post operatively, the intraocular pressure improved to the mid-teens and vision improved to count fingers at 4'with a follow-up of 2 years. CONCLUSION: Pars plana vitrectomy and injection of silicone oil after placement of a Boston Type 1 keratoprosthesis can successfully improve and maintain intraocular pressure in eyes affected by chronic uveitis with ciliary body atrophy and chronic hypotony. This strategy effectively reverses such problems as hypotony maculopathy, disk swelling, scleral infolding, and corneal failure.

Twelve-Month Clinical and Histopathological Performance of a Novel Synthetic Cornea Device in Rabbit Model.

Purpose: To report the biological stability and postoperative outcomes of a second-generation, single-piece, flexible synthetic cornea in a rabbit model. Methods: Device materials and design were amended to enhance biointegration. Optic skirt design devices were made from compact perfluoroalkoxy alkane with porous expanded polytetrafluoroethylene ingrowth surface overlying the skirt and optic wall. Sixteen devices were implanted into intrastromal pocket in rabbit eyes. Rabbits were randomly assigned to 6- and 12-month follow-up cohorts (n = 8 in each) postoperatively. Monthly examinations and optical coherence tomography assessed cornea-device integration, iridocorneal angle, optic nerve, and retina. Results: There were no intraoperative complications. All devices were in situ at exit, with clear optics. No retroprosthetic membrane, glaucoma, cataract formation, or retinal detachment was observed. Two rabbits in the 6-month group had mild, focal anterior lamella thinning without retraction adjacent to the optic near tight sutures. Three postoperative complications occurred in the 12-month group. One rabbit diagnosed with endophthalmitis was euthanized on day 228. Mild sterile focal retraction of anterior lamella occurred in two rabbits, which were terminated on days 225 and 315. Light microscopic examination of enucleated globes demonstrated fibroplasia with new collagen deposition into the porous scaffold without significant inflammation, encapsulation, or granuloma formation. Conclusions: Clinical evaluations, imaging, and histopathological findings indicate favorable outcomes of this synthetic corneal device in a rabbit model. Early feasibility studies in humans are being planned. Translational Relevance: Favorable 12-month results of the device in rabbits demonstrate vision-restoring potential in corneally blind individuals at high risk of failure with donor keratoplasty.

Identification of a novel partial deletion of STS associated with pre-Descemet corneal dystrophy and X-linked ichthyosis.

Purpose: Pre-Descemet corneal dystrophy (PDCD) with X-linked ichthyosis (XLI) is associated with mutations in or deletions of the steroid sulfatase gene (STS). As only three cases of genetically confirmed PDCD associated with XLI have been reported, we sought to expand our understanding of the genetic basis of PDCD by screening STS in two previously unreported families. Materials and Methods: The affected individuals underwent cutaneous and slit-lamp examinations. Saliva samples collected from each affected individual served as a source of DNA for the amplification of the 10 coding exons of STS and flanking DNA markers. Results: The slit-lamp examination of three affected men (two of whom were brothers) from two families revealed bilateral punctate posterior corneal stromal opacities anterior to the Descemet membrane. Cutaneous examination demonstrated dry, coarse, scaly ichthyotic changes characteristic of XLI in all individuals. Genetic examination of the STS locus on the X chromosome in Case 1 revealed a deletion that spanned across DNA markers DXS1130-DXS237, which includes all the coding exons (exons 1-10) of STS. Genetic screening of Cases 2 and 3 revealed a partial deletion of the STS locus involving exons 1-7 and flanking DNA marker DXS1130 on the X chromosome. Conclusions: PDCD with XLI may be associated with either partial or complete deletion of STS. Despite the identification of point mutations, partial deletion, and complete deletion of STS in different affected families reported to date, there was no apparent difference in the affected phenotype between the families, suggesting that the identified variants likely all resulted in loss of function of steroid sulfatase.

Fungal Infection After Descemet Membrane Endothelial Keratoplasty: Incidence and Outcomes.

PURPOSE: The aim of the study was to describe the incidence, presentation, management, and outcomes of fungal infection after Descemet membrane endothelial keratoplasty (DMEK). METHODS: Retrospective case series of culture-proven fungal infections after DMEK reported in the literature, directly by surgeons, and to the Eye Bank Association of America from January 1, 2011, to December 31, 2020. RESULTS: The domestic incidence of fungal infections, fungal keratitis, and fungal endophthalmitis after DMEK from 2011 to 2020 was 3.5, 1.3, and 2.2 per 10,000 cases, respectively, with no significant increasing trend. Thirty-four cases were identified, 14 (41.2%) published and 20 (58.8%) unpublished. Donor tissue fungal cultures were performed in 20 of the 34 (58.8%) cases and were positive in 19 of the 20 (95.0%), all but one Candida species. Recipient fungal cultures were performed in 29 of the 34 (85.3%) cases and were positive in 26 of the 29 (89.7%), all but one Candida species. Infection presented a mean of 33 ± 38 days (median 23, range 2-200, outlier 949) after transplantation: 25 (73.5%) with endophthalmitis and 9 (26.5%) with keratitis. Topical, intrastromal, intracameral, intravitreal, or systemic antifungal therapy was used in all 27 eyes with treatment data. Surgical intervention (DMEK explantation or partial removal, repeat endothelial keratoplasty, penetrating keratoplasty, and/or pars plana vitrectomy) was required in 21 of the 27 (77.8%) eyes. The corrected distance visual acuity at the last follow-up was ≥20/40 in 13 of the 27 (48.1%) eyes and counting fingers or worse in 6 of the 27 (22.2%) eyes. CONCLUSIONS: Fungal infection is a rare but serious complication of DMEK that results in counting fingers or worse corrected distance visual acuity in nearly a quarter of eyes.

Novel DCN Mutation in Armenian Family With Congenital Stromal Corneal Dystrophy.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Prospective, Randomized, Multicenter, Double-Masked, Clinical Trial of Corneal Cross-Linking for Boston Keratoprosthesis Carrier Tissue.

PURPOSE: To assess whether cross-linking the carrier donor cornea of the Boston Keratoprosthesis (BKPro) improves retention of the device in participants at high risk for keratolysis. DESIGN: Prospective, double-masked, randomized clinical trial. METHODS: In this multicenter study, 68 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. The Kaplan-Meier event-free survival was determined by the product-limit method and compared by the log-rank test to examine whether survival curves were different between the CXL and non-CXL groups. The primary outcome of the study was time from surgery to BKPro removal. The secondary endpoint was 12-month retention rate. RESULTS: A total of 68 participants were enrolled and randomized 1:1 to each group. The average age at the time of surgery was 62 (range = 24-89) years, and 42 participants (62%) were male. The overall BKPro retention rate was 70% during a mean follow-up time of 93 (range = 6-201) weeks. Twenty BKPros were removed, 10 in the CXL group and 10 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 = .910). At 12 months, there was no significant difference in the retention rate in the CXL group (94%) vs the non-CXL group (82%, P = .150). CONCLUSIONS: 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.

Infectious Crystalline Keratopathy Secondary to Mycobacterium chelonae.

PURPOSE: 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 . METHODS: 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. RESULTS: 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 . CONCLUSIONS: 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.

Confirmation of association of TGFBI p.Ser591Phe mutation with variant lattice corneal dystrophy.

PURPOSE: To provide the initial confirmation of the c.1772C>T (p.Ser591Phe) mutation in the transforming growth factor-ß-induced (TGFBI) gene as being associated with variant lattice corneal dystrophy (LCD). METHODS: Ophthalmologic examination of the proband was performed with slit lamp biomicroscopy. Saliva was collected as a source of DNA for screening all 17 exons of TGFBI, after which three family members were selectively screened for variants in exon 13. Rosetta-based structure prediction was used to calculate changes in TGFBI protein (TGFBIp) stability secondary to the c.1772C>T (p.Ser591Phe) missense mutation. RESULTS: Slit 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 of TGFBI in the proband revealed a heterozygous missense mutation in exon 13 (c.1772C>T (p.Ser591Phe)) that was also identified in her affected mother but not in her brother or maternal grandmother. Calculated energy change in Rosetta (ΔΔG) for the TGFBIp variant p.Ser591Phe was 23.5, indicating a thermodynamic destabilization resulting from energetic frustration. CONCLUSIONS: The p.Ser591Phe mutation in TGFBI is associated with an unilateral variant of LCD. Rosetta-predicted stability changes indicate that the p.Ser591Phe variant is destabilizing, which is consistent with other observations for LCD-causing mutations.

Infectious keratitis in Vietnam: etiology, organisms, and management at Vietnam National Eye Hospital.

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.

Idiopathic Vitritis after Boston Type 1 Keratoprosthesis Implantation: Incidence, Risk Factors and Outcomes in a Multicentric Cohort.

PURPOSE: To determine incidence, risks factors for, and outcomes of idiopathic vitritis (IV) after Boston type 1 keratoprosthesis (KPro) implantation. METHODS: Retrospective, consecutive case series. Risk factors were analyzed between IV group and No IV group. RESULTS: 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 (all P < .05). By last follow-up, the cumulative proportion of eyes that maintained a visual acuity >20/200 was significantly lower in IV group (P = .01), as was the KPro retention rate (HR = 0.26). CONCLUSIONS: IV 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.

Confirmation of PRDX3 c.568G>C as the Genetic Basis of Punctiform and Polychromatic Pre-Descemet Corneal Dystrophy.

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.

Late Onset Interface Calcium Deposition After Laser In Situ Keratomileusis.

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.

POSTOPERATIVE POSTERIOR SEGMENT COMPLICATIONS AFTER BOSTON TYPE 1 KERATOPROSTHESIS: Incidence, Risk Factors, and Intermediate-Term Outcomes.

PURPOSE: To identify the incidence of, risk factors for, and outcomes of posterior segment complications (PSC) after Boston Type 1 keratoprosthesis (KPro) implantation. METHODS: Retrospective, consecutive case series of KPro procedures at the Stein Eye Institute. Data regarding ocular history, intraoperative details, postoperative management, and outcomes were collected. Eyes with at least one PSC (PSC group) were compared with eyes without PSC (No PSC group), and risk factors for PSC were determined. RESULTS: Ninety-five PSC occurred in 69/169 eyes (40.8%), at a mean of 20.1 months after KPro implantation (0.01 complications/eye month). The median follow-up after KPro implantation was 44.0 months (range 3.0-174.4). The most common PSC were epiretinal membrane (16.6%), cystoid macular edema (12.4%), vitritis (11.2%), and retinal detachment (9.5%). Previous retinal detachment repair, concomitant intraocular lens removal, postoperative aphakia, and vitritis were risk factors for retinal detachment. Postoperative infectious keratitis was a risk factor for epiretinal membrane, cystoid macular edema, and vitritis. The posterior segment complication group had a significantly higher rate of eyes failing to maintain visual acuity ≥20/200 (HR = 2.28; 95% CI = 1.35-3.85) and KPro retention failure rate (HR = 1.66; 95% CI = 0.95-2.91). CONCLUSION: Posterior segment complications occur in approximately 40% of eyes after KPro implantation, resulting in reduced visual outcomes and KPro retention.

Diagnosing Paraproteinemic Keratopathy: A Case Report.

A 65-year-old man presented with bilateral, painless, progressive blurring of vision over 9 years. Slit-lamp examination revealed bilateral subepithelial corneal opacities in clusters located at the mid-periphery. Anterior segment optical coherence tomography, in vivo confocal microscopy (IVCM), serum protein electrophoresis, and molecular genetic testing were performed to evaluate the cause of corneal opacities. Anterior segment optical coherence tomography revealed a band-like, hyperreflective lesion in the Bowman layer and anterior stroma of both corneas. IVCM revealed hyperreflective deposits in the epithelium, anterior stroma, and endothelium. Serum protein electrophoresis identified the presence of paraproteins (immunoglobulin kappa), and molecular genetic testing revealed absence of mutations in the transforming growth factor beta-induced gene (TGFBI) and collagen type XVII alpha 1 gene (COL17A1). The ocular diagnosis of paraproteinemic keratopathy eventually led to a systemic diagnosis of monoclonal gammopathy of undetermined significance by our hematologist/oncologist. Paraproteinemic keratopathy is a rare differential diagnosis in patients with bilateral corneal opacities and therefore may be misdiagnosed as corneal dystrophy or neglected as scars. In patients with bilateral corneal opacities of unknown cause, serological examination, adjunct anterior segment imaging, and molecular genetic testing play a role in establishing the diagnosis.

Corneal ectasia associated with posterior lamellar opacification.

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.

A multi-ethnic genome-wide association study implicates collagen matrix integrity and cell differentiation pathways in keratoconus.

Keratoconus is characterised by reduced rigidity of the cornea with distortion and focal thinning that causes blurred vision, however, the pathogenetic mechanisms are unknown. It can lead to severe visual morbidity in children and young adults and is a common indication for corneal transplantation worldwide. Here we report the first large scale genome-wide association study of keratoconus including 4,669 cases and 116,547 controls. We have identified significant association with 36 genomic loci that, for the first time, implicate both dysregulation of corneal collagen matrix integrity and cell differentiation pathways as primary disease-causing mechanisms. The results also suggest pleiotropy, with some disease mechanisms shared with other corneal diseases, such as Fuchs endothelial corneal dystrophy. The common variants associated with keratoconus explain 12.5% of the genetic variance, which shows potential for the future development of a diagnostic test to detect susceptibility to disease.