No Evidence of Chronic Infection in a Metagenomic Sequencing Study of the Keratoconus Corneal Epithelium.

Objectives: This study aims to assess the presence of pathogenic microorganisms in the corneal epithelial layer of keratoconus patients. Methods: DNA was extracted from corneal epithelial samples procured from ten individual keratoconus eyes and three healthy controls. Metagenomic next-generation sequencing (mNGS) was performed to detect ocular microbiota using an agnostic approach. Results: Metagenomic sequencing revealed a low microbial read count in corneal epithelial samples derived from both keratoconus eyes (average: 530) and controls (average: 622) without a statistically significant difference (p = 0.29). Proteobacteria were the predominant phylum in both keratoconus and control samples (relative abundance: 72% versus 79%, respectively). Conclusions: The overall low microbial read count and the lack of difference in the relative abundance of different microbial species between keratoconus and control samples do not support the hypothesis that a chronic corneal infection is implicated in the pathogenesis of keratoconus. These findings do not rule out the possibility that an acute infection may be involved in the disease process as an initiating event.

Collagen type XII is undetectable in keratoconus Bowman's layer.

PURPOSE: Corneal biomechanical failure is the hallmark of keratoconus (KC); however, the cause of this failure remains elusive. Collagen type XII (COL12A1), which localises to Bowman's layer (BL), is thought to function in stress-bearing areas, such as BL. Given the putative protective role of COL12A1 in biomechanical stability, this study aims to characterise COL12A1 expression in all corneal layers involved in KC. METHODS: TaqMan quantitative PCR was performed on 31 corneal epithelium samples of progressive KC and myopic control eyes. Tissue microarrays were constructed using full-thickness corneas from 61 KC cases during keratoplasty and 18 non-KC autopsy eyes and stained with an antibody specific to COL12A1. Additionally, COL12A1 was knocked out in vitro in immortalised HEK293 cells. RESULTS: COL12A1 expression was reduced at transcript levels in KC epithelium compared with controls (ratio: 0.58, p<0.03). Immunohistochemical studies demonstrated that COL12A1 protein expression in BL was undetectable, with reduced expression in KC epithelium, basement membrane and stroma. CONCLUSIONS: The apparent absence of COL12A1 in KC BL, together with the functional importance that COL12A1 is thought to have in stress bearing areas, suggests that COL12A1 may play a role in the pathogenesis of KC. Further studies are necessary to investigate the mechanisms that lead to COL12A1 dysregulation in KC.

Factors Associated With Receipt of Crosslinking for Keratoconus.

PURPOSE: The aim of this study was to identify factors associated with receipt of standard fluence epithelium-off crosslinking (CXL) for keratoconus (KCN). METHODS: This retrospective, cross-sectional study reviewed electronic health records of treatment-naive patients with KCN seen at the Wilmer Eye Institute between January 2017 and September 2020. Tomographic data were derived from Pentacam (Oculus, Wetzlar, Germany) devices. Multivariable population-average model using generalized estimating equations adjusting for age, sex, race, national area deprivation index, vision correction method, and disease severity was used to identify factors associated with receipt of CXL. RESULTS: From 583 patients with KCN, 97 (16.6%) underwent CXL for KCN. Patients who received CXL in at least 1 eye were significantly younger (mean 24.0 ± 7.8 years) than patients who had never undergone CXL (33.4 ± 9.3 years) ( P < 0.001). In multivariable analysis, Black patients had 63% lower odds of receiving CXL for KCN (OR: 0.37, 95% CI, 0.18-0.79) versus White patients, and older age was protective against receipt of CXL (OR: 0.89 per 1-year increase, 95% CI, 0.86-0.93). Comparison of characteristics by race demonstrated that Black patients presented with significantly worse vision, higher keratometric indices (K1, K2, and Kmax), and thinner corneal pachymetry at baseline versus White or Asian patients. CONCLUSIONS: In this clinical cohort of patients with KCN from a tertiary referral center, Black patients were less likely to receive CXL presumably because of more advanced disease at presentation. Earlier active population screening may be indicated to identify and treat these patients before they become ineligible for treatment and develop irreversible vision loss. Such strategies may improve health equity in KCN management.

Racial Variation in Visual Impairment of Patients With Keratoconus at Presentation.

PURPOSE: This study aimed to investigate racial disparities in the severity of keratoconus (KCN) at presentation, their intersection with socioeconomic variables, and other factors associated with visual impairment. METHODS: This retrospective cohort study examined medical records of 1989 patients (3978 treatment-naive eyes) with a diagnosis of KCN seen at Wilmer Eye Institute between 2013 and 2020. A multivariable regression model adjusting for age, sex, race, insurance type, KCN family history, atopy, smoking status, and vision correction method examined factors associated with visual impairment, defined as a best available visual acuity of worse than 20/40 in the better eye. RESULTS: Demographically, Asian patients were the youngest (33.4 ± 14.0 years) ( P < 0.001), and Black patients had the highest median area deprivation index (ADI) of 37.0 [interquartile range (IQR): 21.0-60.5] ( P < 0.001). Multivariable analysis showed a higher risk of visual impairment for Black (OR 2.25, 95% CI, 1.71-2.95) versus White patients. Medicaid (OR 2.59, 95% CI, 1.75-3.83) and Medicare (OR 2.48, 95% CI, 1.51-4.07) were also associated with a higher odds of visual impairment compared with private insurance, and active smokers were more likely to have visual impairment than those with no prior smoking history (OR 2.17, 95% CI, 1.42-3.30). Eyes of Black patients had the highest maximum keratometry (Kmax) (56.0 ± 11.0D) ( P = 0.003) and the lowest thinnest pachymetry (463.2 ± 62.5 µm) ( P = 0.006) compared with eyes of other races. CONCLUSIONS: Black race, government-funded insurance, and active smoking were significantly associated with increased odds of visual impairment in adjusted analyses. Black race was also associated with higher Kmax and lower thinnest pachymetry, suggesting that Black patients have more severe disease at presentation.

Deep Anterior Lamellar Keratoplasty and Penetrating Keratoplasty for Keratoconus: A Claims-Based Analysis.

PURPOSE: The purpose of this study was to report 1) demographic and clinical characteristics for US patients with keratoconus undergoing deep anterior lamellar keratoplasty (DALK) or penetrating keratoplasty (PK) and 2) complication rates for the 2 procedures. METHODS: We performed a retrospective review of 2010 to 2018 health records for patients with keratoconus age younger than 65 years using the IBM MarketScan Database. A multivariable model adjusting for potential confounders was used to determine factors associated with receiving DALK over PK. Rates of complications 90 days and 1 year postoperatively were calculated. For select complications only (repeat keratoplasty, glaucoma surgery, and cataract surgery), Kaplan-Meier survival curves were additionally constructed over a period of up to 7 years. RESULTS: A total of 1114 patients with keratoconus (mean age: 40.5 ± 12.6 years) were included in the analysis. Hundred nineteen received DALK, and 995 received PK. Regional differences exist, with patients in the north central United States having greater odds of receiving DALK than northeastern patients (OR = 5.08, 95% confidence interval, 2.37-10.90). Rates of endophthalmitis, choroidal hemorrhage, infectious keratitis, graft failure, graft rejection, postoperative cataract, glaucoma, or retinal surgery were all low at 90 days and 1 year. Complication rates for DALK and PK were both low beyond 1 year for repeat keratoplasty, cataract, and glaucoma surgery. CONCLUSIONS: There are regional differences between DALK and PK utilization rates. In addition, DALK and PK complication rates in this nationally representative sample are low at 1 year and beyond, but further studies are needed to assess whether longer-term complications differ by procedure type.

Histological Comparative Analysis of Bowman Layer Grafts Procured Using 3 Different Techniques.

PURPOSE: The objective of this study is to perform a histological analysis of Bowman layer (BL) grafts. METHODS: BL grafts were procured from 13 human cadaver corneal tissues using 3 different donor preparation techniques. Subsequently, the grafts were fixed in 10% buffered formalin phosphate and embedded in paraffin. Hematoxylin and eosin sections of BL grafts were obtained and analyzed under a light microscope. BL and full graft thickness were measured using an image-processing software. RESULTS: All 13 BL grafts contained residual anterior stromal tissue. BL stripping using Kelman-McPherson and Moorfield forceps (technique 3) achieved the thinnest graft thickness with a mean full graft thickness of 18.7 µm (95% confidence interval [CI], -9.8 to 47.2) at the thinnest point of the graft, whereas BL procurement using the Melles lamellar dissector (technique 2) led to the highest mean full graft thickness of 279.9 µm (95% CI, 251.4-308.5) even at the thinnest area of the graft. By contrast, BL dissection using a blunt dissector (technique 1) provided a mean full graft thickness of 70.2 µm (95% CI, 40.4-100.1) at the graft's thinnest point. Although peripheral graft tears occurred in 50%, 50%, and 100% of techniques 1, 2, and 3, respectively, intact 6.25-mm diameter BL grafts could be secured in 50%, 100%, and 80% of techniques 1, 2, and 3, respectively. CONCLUSIONS: None of the techniques used led to the procurement of pure BL grafts devoid of the anterior stroma. Peripheral scoring with a thin needle and tissue manipulation with Kelman-McPherson and Moorfield forceps led to the thinnest grafts in this study.

"Groove and Peel" Deep Anterior Lamellar Keratoplasty: How Deep Can You Go?

PURPOSE: The aim of the current research was to measure the thickness of the residual central corneal bed after performing the manual "Groove and Peel" deep anterior lamellar keratoplasty (GP-DALK) technique on human cadaveric eyes. METHODS: The manual GP-DALK technique was performed on 6 human cadaver eyes by an experienced corneal surgeon. After surgery, the eye globes were fixed in 10% buffered formalin and embedded in paraffin. For each eye, 4-µm-thick hematoxylin and eosin sections involving the pupillary axis were obtained and examined. Using an image-processing software, 2 observers measured the corneal thickness of the residual central corneal bed and the peripheral corneal rims. RESULTS: The overall mean central corneal bed thickness was 35.5 ± 12.9 µm, whereas the mean right and left peripheral rim thicknesses were 993.0 ± 141.1 and 989.3 ± 147.1 µm, respectively ( P = 0.0006 ). In most corneas, the level of dissection reached almost to the pre-Descemetic collagen (Dua) layer. CONCLUSIONS: The GP-DALK technique is effective in removing most of the corneal stroma and may be non-inferior to "big-bubble" deep anterior lamellar keratoplasty in some cases.

Crosslinking vs. Observation in Fellow Eyes of Keratoconus Patients.

Purpose: To evaluate whether unilateral crosslinking (CXL) and conservative follow-up of the fellow eye is an acceptable management strategy in patients with keratoconus (KC). Methods: Seventy-nine fellow eyes of KC subjects that initially underwent unilateral CXL were included. Thirty fellow eyes ultimately received CXL (group 1) whereas 49 fellow eyes were followed (group 2). Best spectacle corrected visual acuity (BSCVA) and corneal tomographic parameters were collected in all eyes preoperatively and at the last follow-up. Results: Subjects who received CXL in the fellow eye (group 1) were younger than subjects who did not (group 2, p=0.026). Group 1 eyes had higher baseline K1 (p=0.026), K2 (p=0.006), Km (p=0.01), and Kmax (p=0.002) compared to group 2 eyes. Amongst the 49 naïve fellow eyes (group 2), 19 eyes showed evidence of progression. Progressing naïve eyes had higher baseline K1, K2, Km, and Kmax (p < 0.01); progressors also had thinner pachymetry at the pupil, apex, and thinnest point (p < 0.01). Baseline values of K1 ≥ 43.5 Diopter (D), K2 > 45.1D, Km > 44.3D, Kmax > 47.9D, astigmatism > 1.4D, pachymetry at the pupil <475 µm, and thinnest pachymetry <478 µm were tentative predictors of progression in the naïve fellow eye. Conclusions: Unilateral CXL with vigilant follow up of the fellow eye may be an acceptable management strategy in a subset of KC eyes.

Keratoplasty in the United States: Trends and Indications From 2015 to 2020.

PURPOSE: The aim of this study was to report trends in keratoplasty techniques and indications in the United States from 2015 to 2020. METHODS: This retrospective review of annual reports from the Eye Bank Association of America assessed domestic corneal graft distribution and surgical indication data for various types of keratoplasty. Trends in procedure volume and indications from 2015 to 2020 were analyzed using the Cochran-Armitage test. RESULTS: The total number of corneal transplants increased from 47,903 in 2015 to 49,143 in 2019, with a decline to 42,257 in 2020, most likely due to COVID-19. Penetrating keratoplasty (PK) volume decreased from 2015 to 2020 (19,160-15,402, 40% to 36.4%, P < 0.001), continuing a trend from the previous decade. Descemet membrane endothelial keratoplasty as a percentage of all keratoplasty procedures increased (9.8%-27.8%, P < 0.001), whereas Descemet stripping automated endothelial keratoplasty (47%-33.9%, P < 0.001) and anterior lamellar keratoplasty (ALK) decreased (2.3%-1.2%, P < 0.001).From 2017 to 2020, repeat corneal transplant was the most common specific indication for PK while ectasias/thinnings decreased in prevalence (15.6%-11.5%, P < 0.001). Ectasias/thinnings and endothelial dystrophy remained the leading indications for ALK and endothelial keratoplasty, respectively. CONCLUSIONS: From 2015 to 2020, keratoplasty trends in the United States showed a continuation of the decrease in PK and increase in Descemet membrane endothelial keratoplasty observed in the previous decade. The most common domestic indications from 2017 to 2020 have been repeat corneal graft, endothelial dystrophy, and ectasias/thinnings for PK, EK, and ALK, respectively.

Predictors of Receiving Keratoplasty for Keratoconus.

PURPOSE: To identify sociodemographic factors and comorbid conditions associated with receiving keratoplasty for keratoconus (KCN). DESIGN: Retrospective, cross-sectional study. METHODS: Health records of KCN patients <65 years of age from 2011 to 2018 were obtained from the IBM MarketScan Database. A multivariable model adjusted for potential confounders was used to examine factors associated with the risk of receiving keratoplasty. RESULTS: Of 42,086 total patients with KCN identified, 1282 (3.0%) patients had keratoplasty to treat KCN. In the fully adjusted analysis, female sex (odds ratio [OR] 0.87 [95% confidence interval {CI} 0.78-0.98]) and living in metropolitan areas (OR 0.75 [95% CI 0.63-0.90]) were associated with lower odds of receiving keratoplasty. Compared with individuals 10 to 19 years of age, those 20 to 29 years of age (OR 1.77 [95% CI 1.31-2.41]) and 30 to 39 years of age (OR 1.61 [95% CI 1.19-2.17]) were more likely to have keratoplasty, while individuals in the older age groups (50-64 years of age) did not show statistically significant associations. Conditions associated with higher odds of receiving keratoplasty were corneal hydrops (OR 4.87 [95% CI 4.07-5.82]), Leber congenital amaurosis (OR 2.41 [95% CI 1.02-5.71]), sleep apnea (OR 1.46 [95% CI 1.25-1.71]), diabetes mellitus (OR 1.32 [95% CI 1.13-1.54]), and depression (OR 1.22 [95% CI 1.03-1.44]). Conditions associated with lower odds were previous contact lens usage (OR 0.61 [95% CI 0.50-0.74]) and a history of glaucoma (OR 0.60 [95% CI 0.49-0.73]). CONCLUSIONS: This analysis of a large sample of patients with KCN reveals previously unidentified risk factors associated with receiving keratoplasty including Leber congenital amaurosis, depression, and diabetes. Future research should examine if young patients with these conditions may benefit from more frequent follow-up and/or early crosslinking to reduce the need for subsequent keratoplasty.

Transcriptomic and Immunohistochemical Analysis of Progressive Keratoconus Reveal Altered WNT10A in Epithelium and Bowman's Layer.

Purpose: To identify global gene expression changes in the corneal epithelium of keratoconus (KC) patients compared to non-KC myopic controls. Methods: RNA-sequencing was performed on corneal epithelium samples of five progressive KC and five myopic control patients. Selected results were validated using TaqMan quantitative PCR (qPCR) on 31 additional independent samples, and protein level validation was conducted using western blot analysis on a subset. Immunohistochemistry was performed on tissue microarrays containing cores from over 100 KC and control cases. WNT10A transcript levels in corneal epithelium were correlated with tomographic indicators of KC disease severity in 15 eyes. Additionally, WNT10A was overexpressed in vitro in immortalized corneal epithelial cells. Results: WNT10A was found to be underexpressed in KC epithelium at the transcript (ratio KC/control = 0.59, P = 0.02 per RNA-sequencing study; ratio = 0.66, P = 0.03 per qPCR) and protein (ratio = 0.07, P = 0.06) levels. Immunohistochemical analysis also indicated WNT10A protein was decreased in Bowman's layer of KC patients. In contrast, WNT10A transcript level positively correlated with increased keratometry (Kmax ρ = 0.57, P = 0.02). Finally, WNT10A positively regulated COL1A1 expression in corneal epithelial cells. Conclusions: A specific Wnt ligand, WNT10A, is reduced at the mRNA and protein level in KC epithelium and Bowman's layer. This ligand positively regulates collagen type I expression in corneal epithelial cells. The results suggest that WNT10A expression in the corneal epithelium may play a role in progressive KC.

Burst Pressures in Eyes with Clear Corneal Incisions Treated with ReSure Glue.

PURPOSE: This study aims to measure burst pressures in 3 mm clear corneal incisions sealed with ReSure, a biodegradable hydrogel sealant, and to compare it to traditional 10-0 nylon sutures and unsealed controls. DESIGN: An ex vivo animal study. METHODS: 3 mm clear corneal incisions were performed in rabbit eyes (ex vivo). The burst pressure was determined, and then, the incisions were sealed with either ReSure glue or a single 10-0 nylon suture. Burst pressure measurements were repeated. RESULTS: Fourteen eyes were included. The median burst pressure in the suture-control group (7 eyes) prior to suture application was 7 mmHg (range: 0-45); the median burst pressure in the 7 glue-controls was 36 mmHg (range: 5-61, p = 0.08 for the comparison of the two control groups). The median burst pressure in the glue group was 93 mmHg (range: 39-129, p = 0.043 when compared to glue-control). The median burst pressure in the suture group was 158 mmHg (range: 70-180, p = 0.018 when compared to suture-control). There was no statistically significant difference in burst pressure values between the glue and suture groups (p = 0.08). CONCLUSION: In this study, ReSure glue applied to 3 mm clear corneal incisions provided sufficient resistance to elevated intraocular pressure when compared to controls. The results of this study suggest that ReSure glue may be comparable to a single 10-0 nylon suture in resisting fluid egress during the early postoperative period.

Post-FDA Approval Results of Epithelium-Off, Full-Fluence, Dresden Protocol Corneal Collagen Crosslinking in the USA.

INTRODUCTION: The purpose of this non-comparative, prospective, observational study was to evaluate the post-US Food and Drug Administration approval outcomes of epithelium-off, full-fluence, Dresden protocol corneal collagen crosslinking (CXL) for the treatment of progressive keratoconus (KCN) and post-refractive corneal ectasia at a US academic tertiary medical center. METHODS: This study involved 125 eyes of 97 patients with KCN and 13 eyes of 12 patients with post-refractive ectasia which underwent CXL between November 2016 and September 2019. Best spectacle-corrected visual acuity (BSCVA) and corneal topographic parameters were measured preoperatively, at postoperative month 1 (POM-1), and between postoperative months 3 and 24 (POM 3-24). RESULTS: Best spectacle-corrected visual acuity, flat keratometry, steep keratometry, and mean corneal power worsened at POM-1 (p < 0.01) with a return to preoperative values at POM 3-24. Maximum keratometry (Kmax) steepened at POM-1 and then improved beyond preoperative levels at POM 3-24 (p < 0.01 and p = 0.03, respectively). Pachymetry at the apex and pupil decreased at POM-1 and POM 3-24 (p = 0.03). Pachymetry at the thinnest point decreased at POM-1 and trended toward reduction at POM 3-24 (p < 0.001 and p = 0.06, respectively). Visual and tomographic outcomes were similar between pediatric and adult populations, and between KCN and post-refractive ectasia patients. CONCLUSIONS: Real-world results of CXL in the USA are similar to those reported in prior studies, demonstrating an initial worsening of BSCVA, pachymetry, and keratometry followed by corneal flattening and preservation of visual acuity. Improvements in Kmax and stability in visual acuity were observed over 24 months in children and adults with progressive KCN or post-refractive ectasia.

Prediction error in iris suture fixated intraocular lenses and long-term stability.

IMPORTANCE: Little evidence exists for prediction error in iris-sutured intraocular lenses. BACKGROUND: To determine the magnitude of prediction error in iris-sutured intraocular lenses, associated factors and their long-term stability. DESIGN: Retrospective, nonrandomized, noncomparative case series conducted at the Wilmer Eye Institute (Baltimore, Maryland, United States). PARTICIPANTS: Adult patients with subluxated intraocular lenses that underwent iris-suture fixation between January 2000 and December 2014 by a single surgeon. Pregnant women, children (below the age of 18) and cases with follow-up under 1 month were excluded. METHODS: Prediction error was calculated in 60 eyes and survival analysis was performed on 99 eyes. MAIN OUTCOME MEASURES: Prediction error (the difference between the postoperative manifest refraction in spherical equivalent and the spherical equivalent predicted by the Barrett Universal II, Holladay 2 and SRK/T formulas), preoperative and postoperative distance-corrected visual acuity, manifest refraction, frequency of postoperative complications and time until re-subluxation. RESULTS: Mean prediction error using the Barrett formula was -0.35 ± 1.0 D. Higher axial length (≥25.5 mm) was associated with greater prediction error (-0.72 ± 1.11 D vs -0.18 ± 0.91 D, P = .048). Twelve re-subluxations occurred over a mean follow-up period of 30.28 ± 41.86 months. The predicted 50% survival of iris-sutured lenses was 114.25 months. CONCLUSIONS AND RELEVANCE: Iris-suture fixation may require moderate lens power adjustment to compensate for prediction error, especially in eyes with higher axial length. Longer follow-up demonstrates that iris-suture fixation remains a viable technique, yet re-subluxations require routine monitoring of such eyes.

ACE2 and TMPRSS2 are expressed on the human ocular surface, suggesting susceptibility to SARS-CoV-2 infection.

PURPOSE: Conjunctival signs and symptoms are observed in a subset of patients with COVID-19, and SARS-CoV-2 has been detected in tears, raising concerns regarding the eye both as a portal of entry and carrier of the virus. The purpose of this study was to determine whether ocular surface cells possess the key factors required for cellular susceptibility to SARS-CoV-2 entry/infection. METHODS: We analyzed human post-mortem eyes as well as surgical specimens for the expression of ACE2 (the receptor for SARS-CoV-2) and TMPRSS2, a cell surface-associated protease that facilitates viral entry following binding of the viral spike protein to ACE2. RESULTS: Across all eye specimens, immunohistochemical analysis revealed expression of ACE2 in the conjunctiva, limbus, and cornea, with especially prominent staining in the superficial conjunctival and corneal epithelial surface. Surgical conjunctival specimens also showed expression of ACE2 in the conjunctival epithelium, especially prominent in the superficial epithelium, as well as the substantia propria. All eye and conjunctival specimens also expressed TMPRSS2. Finally, western blot analysis of protein lysates from human corneal epithelium obtained during refractive surgery confirmed expression of ACE2 and TMPRSS2. CONCLUSIONS: Together, these results indicate that ocular surface cells including conjunctiva are susceptible to infection by SARS-CoV-2, and could therefore serve as a portal of entry as well as a reservoir for person-to-person transmission of this virus. This highlights the importance of safety practices including face masks and ocular contact precautions in preventing the spread of COVID-19 disease.

ACE2 and TMPRSS2 are expressed on the human ocular surface, suggesting susceptibility to SARS-CoV-2 infection.

PURPOSE: Conjunctival signs and symptoms are observed in a subset of patients with COVID-19, and SARS-CoV-2 has been detected in tears, raising concerns regarding the eye both as a portal of entry and carrier of the virus. The purpose of this study was to determine whether ocular surface cells possess the key factors required for cellular susceptibility to SARS-CoV-2 entry/infection. METHODS: We analyzed human post-mortem eyes as well as surgical specimens for the expression of ACE2 (the receptor for SARS-CoV-2) and TMPRSS2, a cell surface-associated protease that facilitates viral entry following binding of the viral spike protein to ACE2. RESULTS: Across all eye specimens, immunohistochemical analysis revealed expression of ACE2 in the conjunctiva, limbus, and cornea, with especially prominent staining in the superficial conjunctival and corneal epithelial surface. Surgical conjunctival specimens also showed expression of ACE2 in the conjunctival epithelium, especially prominent in the superficial epithelium, as well as weak or focal expression in the substantia propria. All eye and conjunctival specimens also expressed TMPRSS2. Finally, Western blot analysis of protein lysates from human corneal epithelium obtained during refractive surgery confirmed expression of ACE2 and TMPRSS2. CONCLUSIONS: Together, these results suggest that ocular surface cells including conjunctiva are susceptible to infection by SARS-CoV-2, and could therefore serve as a portal of entry as well as a reservoir for person-to-person transmission of this virus. This highlights the importance of safety practices including face masks and ocular contact precautions in preventing the spread of COVID-19 disease.

The Correlation between Corneal Findings and Disease Severity in Keratoconus per Scheimpflug Corneal Tomography.

PURPOSE: This study aims to correlate the clinical signs of keratoconus (KC) which include superficial apical scarring, Fleischer rings, and Vogt striae with best spectacle-corrected visual acuity (BSCVA) and corneal tomography findings. Patients and methods. A retrospective observational study. 72 consecutive KC patients seen by the senior author over the course of one year were included in this case series. Eyes with pellucid marginal degeneration, postrefractive ectasia, history of a corneal graft, prior corneal collagen cross-linking, intracorneal ring segments or hydrops were excluded from analysis. Subsequently, the final analysis included only treatment-naïve KC eyes with varying degrees of disease severity. RESULTS: BSCVA with manifest refraction was 0.5 logMAR higher in eyes with apical scarring (p < 0.001). Eyes with apical scarring had worse vision than eyes with Fleischer rings alone (0.43 logMAR higher in the former, p < 0.001). Eyes with apical scarring had worse vision than eyes with Fleischer rings alone (0.43 logMAR higher in the former, K2 = 64.56 ± 12.89 D versus 49.07 ± 6.61 D, p < 0.001). Eyes with apical scarring had worse vision than eyes with Fleischer rings alone (0.43 logMAR higher in the former, K2 = 64.56 ± 12.89 D versus 49.07 ± 6.61 D, p < 0.001). Eyes with apical scarring had worse vision than eyes with Fleischer rings alone (0.43 logMAR higher in the former, K2 = 64.56 ± 12.89 D versus 49.07 ± 6.61 D, p < 0.001). Eyes with apical scarring had worse vision than eyes with Fleischer rings alone (0.43 logMAR higher in the former, p < 0.001). Eyes with apical scarring had worse vision than eyes with Fleischer rings alone (0.43 logMAR higher in the former, p < 0.001). Eyes with apical scarring had worse vision than eyes with Fleischer rings alone (0.43 logMAR higher in the former, p < 0.001). Eyes with apical scarring had worse vision than eyes with Fleischer rings alone (0.43 logMAR higher in the former. CONCLUSION: The presence of apical scarring and Fleischer rings on biomicroscopy can aid the clinician in making the distinction between severe or long-standing disease (respectively). Apical scarring is a sign of advanced disease and is associated with worse BSCVA and tomography findings. Fleischer rings are markers of intermediate disease and their presence correlates with disease duration.

Combined Protocols for Corneal Collagen Cross-Linking with Photorefractive Surgery for Refractive Management of Keratoconus: Update on Techniques and Review of Literature.

With the development and gradual dissemination of corneal collagen cross-linking (CXL) in the twenty-first century as an early treatment for keratoconus, the management paradigm has shifted to include a greater focus on complete refractive correction for these patients. Though supplemental hard contact lens therapy remains a mainstay of visual rehabilitation in keratoconus, there has been increasing appeal in a completely surgical approach by combining CXL with adjuvant refractive procedures to both halt the ectatic process and enhance functional visual outcomes. Collectively termed "CXL plus" procedures, several combined protocols have been studied to various degrees in conjunction with CXL, involving photorefractive keratectomy (PRK), transepithelial phototherapeutic keratectomy (PTK), conductive keratoplasty (CK), intrastromal corneal ring segments (ICRS) implantation, phakic intraocular lens (PIOL) implantation, or multiple of these techniques together. The scope of this review aims to encompass a summary of current CXL protocols and present the current status of studies involving adjunctive keratorefractive procedures combined with CXL. By discussing the results to date of these CXL plus protocols, we can assess what further areas of investigation are necessary within this field as the next step to optimizing treatment modalities and outcomes for our keratoconus patients, regardless of disease severity.

Diffuse lamellar keratitis after epi-off corneal crosslinking: An under-recognized complication?

PURPOSE: To report diffuse lamellar keratitis (DLK) occurring in an eye that underwent epithelium-off (epi-off) corneal cross-linking (CXL) as a treatment for post-surgical ectasia and the successful treatment of progressive ectasia with a novel epi-on CXL and conductive keratoplasty (CK) treatment. OBSERVATIONS: A 42-year-old man presented with corneal ectasia in his right eye 3 years after laser in situ keratomileusis (LASIK) surgery. He underwent epi-off corneal CXL using the Dresden protocol. Grade II DLK was diagnosed within days of CXL. Despite successful treatment of DLK, best-corrected visual acuity in the right eye deteriorated over the next 4 months due to progression of ectasia and remained worse than the patient's pre-operative baseline 1 year after epi-off CXL. Because of apparent disease progression, despite his CXL treatment, the patient underwent a novel, transepithelial CXL (TE-CXL) treatment combined with conductive keratoplasty (CK). This treatment improved his vision and stabilized his ectasia without subsequent DLK. Approximately 3 years after CK and TE-CXL, his eye remains stable with 4 Snellen lines of improved vision and no progression of ectasia. CONCLUSION AND IMPORTANCE: Epithelium-off CXL is used increasingly to treat post-LASIK ectasia. First, in this case, DLK occurred after epi-off CXL. We suggest careful scrutiny of such cases as DLK is difficult to identify after epi-off CXL. Second, the epi-off CXL was unsuccessful in stopping the post-LASIK ectasia. Transepithelial CXL successfully treated the ongoing ectasia after resolution of the DLK with no subsequent re-occurrence of DLK. We suggest that TE-CXL may provide a successful initial treatment for post-LASIK ectasia that also minimizes the epithelial disruption that can lead to DLK.