The outcomes of corneal sight rehabilitating surgery in Stevens-Johnson syndrome: case series.

PURPOSE: To summarize the outcomes of corneal sight rehabilitating surgery in Stevens-Johnson syndrome (SJS). METHODS: This is a retrospective analysis of a consecutive case series. Twenty-four eyes of 18 SJS patients were included in this study. The ocular parameters, surgical procedures, postoperative complications, and additional treatments of the cases were reviewed. RESULTS: A total of 29 corneal sight rehabilitating surgeries, which consists of 9 keratoplasties, 8 Keratolimbal allograft (KLAL) and 12 combined surgeries (keratoplasty and KLAL simultaneously) were performed on the 24 eyes. All patients were treated with glucocorticoid eyedrops and tacrolimus eyedrops for anti-rejection treatment without combining systemic immunosuppression, except two patients who were prescribed prednisone tablets for the management of systemic conditions. The mean follow-up period was 50.6 ± 28.1 months. The optimal visual acuity (VA) (0.74 ± 0.60 logarithm of the minimum angle of resolution [logMAR]) and endpoint VA (1.06 ± 0.82 logMAR) were both significantly better than the preoperative VA (1.96 ± 0.43 logMAR) (95% CI, p = 0.000). 57.1% patients (8/14) were no longer in the low vision spectrum, and 88.9% patients (8/9) were no longer blind. The mean epithelialization time was 7.1 ± 7.6 weeks. The success rate was 86.7%. Additional treatments for improving epithelialization included administration of serum eyedrops (n = 10), contact lens (n = 15), amniotic membrane transplantation (n = 6), and tarsorrhaphy (n = 8). Complications included delayed epithelialization (n = 4, over 12 weeks), glaucoma (n = 11), and severe allograft opacity (n = 4). Only one graft rejection was observed. CONCLUSIONS: Keratoplasty and KLAL can remarkably enhance VA and improve low vision or even eliminate blindness for ocular complications of SJS. The outcome of the surgeries was correlated with the preoperative ocular situation and choice of operative methods.

Incidence of Cytomegalovirus Infection After Repeat Keratoplasty and Associated Rate of Graft Failure.

INTRODUCTION: The aim of this work was to compare the prognosis and characteristics of patients with Cytomegalovirus (CMV) infection (CMV+) with those of patients without virus infection (Virus-) undergoing repeat keratoplasty. METHODS: This prospective propensity score-matched cohort study enrolled patients who underwent repeat keratoplasty for graft failure at the Peking University Third Hospital between January 2016 and May 2022. Patients with prior viral keratitis before the first keratoplasty were excluded. The primary outcome measure was the graft failure rate. The secondary outcome measures included the anterior segment characteristics, intraocular pressure (IOP), and endothelial cell density. RESULTS: Ninety-four matched patient pairs were included. The graft failure rate in the CMV+ group (71%) was higher than that in the Virus- group (29%) (P < 0.001). CMV infection in the cornea increased the risk of repeat graft failure and shortened the median survival time (hazard ratio, 3.876; 95% confidence intervals, 2.554-5.884; P < 0.001). The characteristics of graft failure included exacerbation of ocular surface inflammation, neovascularization, and opacification. Epithelial defects, high IOP, and endothelial decompensation were observed at an increased frequency in the CMV+ group (all P < 0.005). Recurrent CMV infection presented as early endothelial infection in the CMV+ group. Recurrence of CMV infection was confined to the graft endothelium without involving the stroma and epithelium post-repeat endothelial keratoplasty. CONCLUSIONS: CMV infection post-keratoplasty leads to persistent endothelial damage and graft opacification and significantly increases the risk of repeat graft failure. Localized recurrence of CMV infection in the endothelial grafts underscores the importance of monitoring and treatment. TRIAL REGISTRATION: Chictr.org.cn, ChiCTR1800014684.

Water-Free Cyclosporine Ophthalmic Solution vs Vehicle for Dry Eye Disease: A Randomized Clinical Trial.

Importance: Dry eye disease (DED) is a prevalent eye disorder. Cyclosporine is an effective immunomodulator that is widely used in DED; however, due to its highly hydrophobic nature, delivery of cyclosporine to the ocular surface is challenging. Objective: To evaluate the efficacy and safety of SHR8028, a water-free cyclosporine ophthalmic solution, 0.1%, compared with vehicle in Chinese participants with DED. Design, Setting, and Participants: This was a multicenter, double-blind, vehicle-controlled, phase 3 randomized clinical trial conducted from March 4, 2021, to July 22, 2022. Adult participants with moderate to severe DED were recruited from 12 hospitals in China. Study data were analyzed April 2, 2022, for the primary analysis. Interventions: Following a 14-day run-in period with an artificial tear, participants were randomly assigned (1:1) to receive water-free cyclosporine or vehicle (1 eye drop in each eye twice daily). After a 29-day treatment, participants of both groups were given the option to receive water-free cyclosporine for an additional 12 weeks for longer-term safety assessment. Main Outcomes and Measures: The primary end points were changes from baseline in total corneal fluorescein staining (tCFS) using the National Eye Institute scale and in dryness score on a visual analog scale at day 29. Results: A total of 206 participants (mean [SD] age, 47.8 [14.2] years; 185 female [90%]) were enrolled, with 103 each in the cyclosporine group and the vehicle group. At day 29, the cyclosporine group experienced improved tCFS compared with vehicle (change [Δ] = -1.8; 95% CI, -2.7 to -1.0; P < .001), with a tCFS score decrease from baseline of -4.8 in the cyclosporine group and -3.0 in the vehicle group. Dryness score decreased from baseline in both groups (-19.2 vs -15.4; Δ = -3.8; 95% CI, -9.2 to 1.6; P = .17). During the 29-day treatment, treatment-related adverse events were reported in 15 participants (14.6%) in the cyclosporine group and 11 participants (10.7%) in the vehicle group. Conclusions And Relevance: Results demonstrated superiority of a water-free cyclosporine, 0.1%, eye solution over vehicle in improving tCFS score at day 29 in Chinese participants with DED. However, dryness score (VAS) was not improved at day 29. Trial Registration: ClinicalTrials.gov Identifier: NCT05841043.

Cytokine analysis of aqueous humor in patients with cytomegalovirus corneal endotheliitis.

PURPOSE: To evaluate cytokine levels of aqueous humor in patients with cytomegalovirus (CMV) corneal endotheliitis and their relationships with CMV DNA load. METHODS: 44 aqueous humor samples were obtained from 26 patients with CMV corneal endotheliitis at various stages of treatment. 33 samples obtained from cataract patients during the same period were selected as a control group. Each sample was used to measure the concentration of the CMV DNA load using real-time quantitative polymerase chain reaction, and to examine the levels of IL-6, IL-8, IL-10, MCP-1, VCAM-1, VEGF, IP-10, G-CSF, ICAM-1 and IFN-γ using a cytometric bead array. RESULTS: All 10 cytokines were found to have statistically significant differences between the CMV endotheliitis and cataract groups. The Spearman correlation test showed that the concentration of CMV DNA load was significantly associated with the levels of IL-6 (P = 0.005, r = 0.417), IL-8 (P < 0.001, r = 0.514), IL-10 (P < 0.001, r = 0.700), MCP-1 (P = 0.001, r = 0.487), VEGF (P < 0.001, r = 0.690), IP-10 (P = 0.001, r = 0.469), G-CSF (P < 0.001, r = 0.554) and ICAM-1 (P < 0.001, r = 0.635), but not significantly associated with VCAM-1 (P = 0.056) and IFN-γ (P = 0.219). CONCLUSIONS: There was a combined innate and adaptive immune response in aqueous humor in patients with CMV endotheliitis. Levels of multiple cytokines were significantly correlated with viral particle. Cytokines are potential indicators to help diagnose CMV endotheliitis, evaluate disease activity and assess treatment response.

A New Treatment for Recalcitrant Neurotrophic Keratopathy of Ocular Graft-Versus-Host Disease with Virus Infection.

INTRODUCTION: Neurotrophic keratopathy (NK) is a rare degenerative ocular disease that can be difficult to treat. There were no effective resolutive treatments for severe NK caused by ocular graft-versus-host disease (oGVHD) along with virus infection. To address this question, we designed a prospective cohort study to evaluate the efficacy and safety of topical recombinant human nerve growth factor (rhNGF) in patients with recalcitrant NK of oGVHD and viral infection. METHODS: This prospective cohort study enrolled patients with recalcitrant NK diagnosed with oGVHD and treated with rhNGF. Clinical evaluations included the range of epithelial defects, best corrected visual acuity, intraocular pressure, slit-lamp examination, and corneal fluorescein staining. Examinations of the central corneal thickness, corneal sensitivity, and nerve fiber regeneration were performed at each visit at 4, 8, 12, 20 weeks and 6 months, respectively, after initiating rhNGF treatment. RESULTS: All enrolled patients were diagnosed with NK at stage 2 (7 eyes, 63.6%) or stage 3 (4 eyes, 36.4%) and responded to rhNGF treatment. Five of 11 (45.5%) and 9 of 11 eyes (81.8%) achieved complete corneal epithelial healing after 4 and 8 weeks, respectively. All 11 eyes (100%) achieved complete corneal healing after 12 weeks. There was also a significant reduction in the corneal ulcer area during each visit (P < 0.001), as well as in the corneal fluorescein staining score (P < 0.010). There was a significant improvement in corneal sensation when compared to the baseline (P < 0.050). CONCLUSION: Topical treatment with rhNGF effectively promoted the complete corneal healing of persistent epithelial defects and corneal ulcers in patients with recalcitrant NK in oGVHD and viral infection.

Deep Anterior Lamellar Keratoplasty-Treated Keratoconic Eyes With Descemet Membrane Rupture.

PURPOSE: The aim of this study was to evaluate the outcomes of deep anterior lamellar keratoplasty (DALK) and compare it with penetrating keratoplasty (PKP) in keratoconic eyes with Descemet membrane (DM) rupture. METHODS: In this comparative retrospective case series, 33 keratoconic eyes with a history of hydrops underwent DALK and 27 received PKP. Baseline and postoperative visual acuity, corneal astigmatism, mean keratometry, endothelial cell density, and complication rates were measured. RESULTS: The median follow-up of patients who underwent DALK was 45 months (range, 4-76 months) and that of patients who underwent PKP was 84 months (range, 4-136 months). Both procedures had comparable postoperative visual acuity, astigmatism, and mean keratometry. Significantly higher endothelial cell densities were observed in DALK than in PKP at 2, 3, and 5 years postsurgery (2043 ± 767 vs. 1165 ± 683 cell/mm2, P = 0.007, n = 12 in both groups at 2 years). Intra-DALK, 15 perforations occurred (44.12%) and 1 (2.94%) was converted to PKP. Graft rejection was diagnosed in 1 (3.03%) DALK procedure versus 8 (29.63%) PKP (P = 0.008), and other long-term complication rates were equivalent. Kaplan-Meier survival analysis also revealed a higher rejection-free survival rate for the DALK group (P = 0.012). Subgroup analysis within both groups based on the severity of preoperative DM rupture revealed no significant difference in any major 2-year outcomes. CONCLUSIONS: DALK showed similar beneficial visual outcome and safety but significantly better endothelial protection over PKP in eyes with keratoconus and previous hydrops. Therefore, DALK is recommended in posthydrops cases irrespective of the DM rupture severity.

Development and validation of a diagnostic model for the identification of chronic ocular graft-versus-host disease (oGVHD).

Purpose: To verify the International Chronic Ocular Graft-Versus-Host Disease (ICCGVHD) Group diagnostic criteria and establish an easy-to-use and reliable diagnosis model for quick identification of chronic oGVHD. Methods: This study included 180 patients (355 eyes) who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) and visited the Peking University Third Hospital Cornea and Ocular Surface Disease Specialist Clinic from July 2020 to February 2021. The proportion of chronic oGVHD was 76.06% (279/355). Results: Five complaints, including eye dryness, photophobia, foreign body sensation, eye redness, and burning sensation; six ophthalmic examinations, including Ocular Surface Disease Index (OSDI) score, corneal fluorescein staining (CFS), tear break-up time (TBUT), Schirmer's test score without anesthesia, conjunctival score, tear meniscus height, and non-ocular GVHD-involved organs were significantly different between patients with chronic oGVHD and control group (p < 0.05). Binary logistic regression (backward LR algorithm) selection demonstrated that three variables retained diagnostic significance for chronic oGVHD: CFS (OR = 2.71 (1.92-3.81), p < 0.001), Schirmer's test score without anesthesia (OR = 0.83 (0.76-0.91), p < 0.001), and conjunctival score (OR = 1.96 (1.13-3.42), p = 0.031). A nomogram for the identification of chronic oGVHD was developed, and its performance was examined using an internal validation cohort (118 eyes). The areas under the curve (AUCs) for the three-variable-based nomogram were 0.976 (95% CI (0.959-0.992), p < 0.01) and 0.945 (95% CI (0.904-0.986), p < 0.01) in the development and internal validation cohorts, respectively. Conclusion: This concise three-variable-based nomogram based on ICCGVHD criteria could serve as an easy-to-use and reliable tool for rapid screening of chronic oGVHD.

Three-dimensional in vivo evaluation of the cornea in patients with unilateral posterior interstitial keratitis.

Purpose: The purpose of this study was to investigate the in vivo morphologic features of the cornea in patients with unilateral posterior interstitial keratitis. Methods: Seven eyes of 7 patients with unilateral posterior interstitial keratitis were examined by slit-lamp biomicroscopy, anterior segment optical coherence tomography (AS-OCT), and in vivo confocal microscopy (IVCM). The imaging features of the cornea were evaluated and analyzed. Results: By slit-lamp examination, the posterior corneal stromal opacities were observed in all 7 eyes, and deep neovascularization in 4 eyes. The posterior stromal opacities showed higher reflectivity with an intact overlying epithelium by AS-OCT and did not invade the Bowman's layer in all cases. IVCM revealed highly reflective dispersed microdots, needle-shaped bodies, and increased reflectivity of keratocytes in the lesion site in all patients. Active Langerhans cells and an attenuated subbasal nerve plexus were observed in 5 eyes. After treatment, the active Langerhans cells disappeared; however, highly reflective microdots and needle-shaped bodies remained. Conclusion: The three-dimensional evaluation of slit-lamp biomicroscopy, AS-OCT, and IVCM may help in the early diagnosis of patients with posterior interstitial keratitis.

Comparison of Femtosecond Laser Assistance and Manual Trephination in Deep Anterior Lamellar Keratoplasty in the Treatment of Keratoconus: A Meta-Analysis.

PURPOSE: To compare the efficacy and safety of femtosecond laser-assisted deep anterior lamellar keratoplasty (F-DALK) with those of manual-trephination DALK (M-DALK) in treating keratoconus. DESIGN: Systematic review and meta-analysis. METHODS: Through November 2022, we comprehensively searched PubMed, EMBASE, the Cochrane Library, and 4 Chinese databases. Studies that involved comparisons between F-DALK and M-DALK groups and that reported on relevant efficacy and/or safety parameters were included. Primary outcomes were uncorrected- and corrected-distance visual acuity and intraoperative complication rates. Secondary outcomes were spherical equivalent, topographic astigmatism, refractive cylinder, mean keratometry, endothelial cell density, suture removal time, and postoperative complication rates. These data were analyzed using Cochrane Review Manager software version 5.3. RESULTS: This meta-analysis included 9 nonrandomized controlled studies involving 1713 eyes. In eyes treated with F-DALK, corrected-distance visual acuity at 1 to 6 months (weighted mean difference = -0.07 [95% confidence interval {CI} -0.10 to -0.03]; I2 = 0%; P < .001) after surgery was better and intraoperative Descemet membrane perforation occurred less often (odds ratio = 0.53 [95% CI 0.31-0.92]; I2 = 6%; P = .02) than in eyes treated with M-DALK. No clinically significant differences in other outcomes were found among the groups. CONCLUSIONS: Both F-DALK and M-DALK are safe and efficacious for patients with keratoconus. Compared with M-DALK, F-DALK can provide better early visual acuity and reduce the intraoperative perforation rate, and its likely improvements to long-term visual quality and endothelial cell preservation warrant further investigation. In addition, the 2 techniques seem to be comparable regarding refractive outcomes and other complications.

Spokewise iridotomy combined with Descemet stripping automated endothelial keratoplasty in iridocorneal endothelial syndrome.

Purpose: Iridocorneal endothelial (ICE) syndrome is a progressive anterior segment disorder that can be tricky to treat. Keratoplasty is commonly used to treat corneal edema in ICE syndrome. However, glaucoma is an important risk factor affecting graft survival. To address this question, we designed a retrospective cohort study to evaluate the effect of Spokewise Iridotomy (SI) on Descemet Stripping Automated Endothelial Keratoplasty (DSAEK) Grafts in Iridocorneal Endothelial (ICE) Syndrome. Methods: This was a retrospective cohort study. A total of 29 patients were included; 31 eyes with ICE syndrome underwent DSAEK at Peking University Third Hospital between June 2015 and June 2022, including 11 eyes with combined SI during DSAEK. The aim was to explore the effect of SI on vision, glaucoma control, complications, peripheral anterior synechiae recurrence, endothelial cell count, and graft survival. Results: The median follow-up time was 30.83 months (mo.) in the SI+Endothelial Keratoplasty (EK) group and 6.17 mo in the EK group. The 2-year cumulative survival rate of grafts in the SI+EK group was 100%, compared with the 6-month and 1-year cumulative survival rates of 80.2 and 63.2%, respectively, in the EK group (p = 0.043). The SI+EK group had a lower incidence of immediate postoperative complications (p = 0.005), fewer postoperative anti-glaucoma medications (AGMs) (p = 0.029), smaller peripheral anterior synechiae recurrence (p = 0.001), and significant visual acuity improvement (p < 0.05). More AGMs were used in failed grafts (p = 0.002). Conclusion: SI can help control intraocular pressure, improve visual acuity, and increase graft survival after DSAEK in ICE syndrome patients.

Assessing abnormal corneal endothelial cells from in vivo confocal microscopy images using a fully automated deep learning system.

BACKGROUND: The goal of this study is to develop a fully automated segmentation and morphometric parameter estimation system for assessing abnormal corneal endothelial cells (CECs) from LASER in vivo confocal microscopy (IVCM) images. METHODS: First, we developed a fully automated deep learning system for assessing abnormal CECs using a previous development set composed of normal images and a newly constructed development set composed of abnormal images. Second, two testing sets, one with 169 normal images and the other with 211 abnormal images, were used to evaluate the clinical validity and effectiveness of the proposed system on LASER IVCM images with different corneal endothelial conditions, particularly on abnormal images. Third, the automatically calculated endothelial cell density (ECD) and the manually calculated ECD were compared using both the previous and proposed systems. RESULTS: The automated morphometric parameter estimations of the average number of cells, ECD, coefficient of variation in cell area and percentage of hexagonal cells were 257 cells, 2648 ± 511 cells/mm2, 32.18 ± 6.70% and 56.23 ± 8.69% for the normal CEC testing set and 83 cells, 1450 ± 656 cells/mm2, 34.87 ± 10.53% and 42.55 ± 20.64% for the abnormal CEC testing set. Furthermore, for the abnormal CEC testing set, Pearson's correlation coefficient between the automatically and manually calculated ECDs was 0.9447; the 95% limits of agreement between the manually and automatically calculated ECDs were between 329.0 and - 579.5 (concordance correlation coefficient = 0.93). CONCLUSIONS: This is the first report to count and analyze the morphology of abnormal CECs in LASER IVCM images using deep learning. Deep learning produces highly objective evaluation indicators for LASER IVCM corneal endothelium images and greatly expands the range of applications for LASER IVCM.

Assessment of Corneal Epithelial Changes and Related Factors in Ocular Chronic Graft-Versus-Host Disease (GVHD) by in Vivo Confocal Microscopy.

PURPOSE: To evaluate corneal epithelial changes and related factors in chronic ocular graft-versus-host disease (oGVHD) patients. METHODS: 21 patients (35 eyes) with chronic oGVHD and 8 patients (12 eyes) without oGVHD after bone marrow transplantation were recruited for assessment involving in vivo confocal microscopy (IVCM) analysis, ocular surface parameter determination and tear cytokine level analysis. The IVCM corneal epithelial scoring system was used to evaluate corneal epithelial changes. RESULTS: There was a significant difference in the corneal epithelial score (p = .001) between the two groups. The corneal epithelial scores were significantly correlated with the corneal fluorescein staining scores (CFS, r = 0.463, p < .001), Schirmer's test (r = -0.389, p = .009) and tear cytokine levels of EGF (r = -0.491, p < .001) and APRIL (r = -0.318, p = .030). CONCLUSIONS: The depth of corneal epithelial defects can be estimated by the CFS. Corneal epithelial changes of chronic oGVHD are considered to be associated with lacrimal deficiency and a lack of EGF.

Destructive effects on endothelial cells of grafts in cytomegalovirus DNA-positive patients after keratoplasty.

AIM: To investigate corneal graft survival rate and endothelial cell density (ECD) loss after keratoplasty in cytomegalovirus (CMV) positive patients. METHODS: This was a retrospective cohort study. We analyzed the clinical data of patients who underwent viral DNA detection in aqueous humor/corneal tissue collected during keratoplasty from March 2015 to December 2018 at the Peking University Third Hospital, Beijing, China. To further evaluate the effect of CMV on graft survival rate and ECD loss, patients were divided into three groups: 1) CMV DNA positive (CMV+) group; 2) viral DNA negative (virus-) group, comprising virus- group eyes pairwise matched to eyes in the CMV+ group according to ocular comorbidities; 3) control group, comprising virus- group eyes without ocular comorbidities. The follow-up indicators including graft survival rate, ECD, ECD loss, and central corneal thickness (CCT), were analyzed by Tukey honestly significant difference (HSD) test. RESULTS: Each group included 29 cases. The graft survival rate in CMV+ group were lowest among the three groups (P=0.000). No significant difference in donor graft ECD was found among three groups (P=0.54). ECD in the CMV+ group was lower than the virus- group at 12 (P=0.009), and 24mo (P=0.002) after keratoplasties. Furthermore, ECD loss was higher in the CMV+ group than in the virus- group in the middle stage (6-12mo) post-keratoplasty (P=0.017), and significantly higher in the early stage (0-6mo) in the virus- group than in the control group (P=0.000). CONCLUSION: CMV reduces the graft survival rate and exerts persistent detrimental effects on the ECD after keratoplasty. The graft ECD loss associate with CMV infection mainly occurrs in the middle stage (6-12mo postoperatively), while ocular comorbidities mainly affects ECD in the early stage (0-6mo postoperatively).

Clinical Manifestations and Long-term Outcomes of Endothelial Keratoplasty in Patients with Proven VZV-related Endothelial Decompensation.

PURPOSE: To report the clinical manifestations, postoperative complications and long-term outcomes of endothelial keratoplasty in VZV-related endothelial decompensation. METHODS: In this retrospective study, thirteen eyes undergoing endothelial keratoplasty (EK) for VZV-related endothelial decompensation were compared with controls for Fuchs endothelial dystrophy or pseudophakic bullous keratopathy. RESULTS: Twelve patients did not have typical dermal pain or blisters. Ten patients had obvious iris abnormalities. Glaucoma was noted in eight patients before surgery. The best spectacle-corrected visual acuity improved from 1.12 ± 0.47 to 0.39 ± 0.43 (p = .002), whereas endothelial cell (EC) loss was 65% ±15% at 12 months that higher than that in the controls (p < .05). Postoperative complications included graft detachment (2/13), recurrence of endotheliitis (3/13), neurotrophic ulcer (1/13) and scleritis (1/13). CONCLUSIONS: The onset of VZV-related endothelial decompensation is generally insidious. Iris segmental atrophy, glaucoma and pigment KPs are highly suspected to be associated with VZV. EK is a reasonable option to rehabilitate vision.

Fully automated grading system for the evaluation of punctate epithelial erosions using deep neural networks.

PURPOSE: The goal was to develop a fully automated grading system for the evaluation of punctate epithelial erosions (PEEs) using deep neural networks. METHODS: A fully automated system was developed to detect corneal position and grade staining severity given a corneal fluorescein staining image. The fully automated pipeline consists of the following three steps: a corneal segmentation model extracts corneal area; five image patches are cropped from the staining image based on the five subregions of extracted cornea; a staining grading model predicts a score for each image patch from 0 to 3, and automated grading score for the whole cornea is obtained from 0 to 15. Finally, the clinical grading scores annotated by three ophthalmologists were compared with automated grading scores. RESULTS: For corneal segmentation, the segmentation model achieved an intersection over union of 0.937. For punctate staining grading, the grading model achieved a classification accuracy of 76.5% and an area under the receiver operating characteristic curve of 0.940 (95% CI 0.932 to 0.949). For the fully automated pipeline, Pearson's correlation coefficient between the clinical and automated grading scores was 0.908 (p<0.01). Bland-Altman analysis revealed 95% limits of agreement between the clinical and automated grading scores of between -4.125 and 3.720 (concordance correlation coefficient=0.904). The average time required for processing a single stained image during pipeline was 0.58 s. CONCLUSION: A fully automated grading system was developed to evaluate PEEs. The grading results may serve as a reference for ophthalmologists in clinical trials and residency training procedures.

Tear Cytokines Associated With Therapeutic Effects in Chronic Ocular Graft-Versus-Host Disease.

PURPOSE: The local application of antiinflammatory and immunosuppressive agents is an effective method for the treatment of ocular graft-versus-host disease (oGVHD); however, we noticed that some patients with oGVHD did not respond to topical therapy as well as many others. This study aimed to determine whether tear cytokines were associated with therapeutic effects in oGVHD. METHODS: Forty patients with chronic oGVHD were enrolled and grouped as responders (n = 24) and nonresponders (n = 16) based on the clinical response to 1 month of topical treatment. Tear samples were collected from each participant before and after treatment, and the tear concentrations of 7 cytokines (IL-2, IL-6, IL-8, IL-10, IL-17A, TNF-α, and ICAM-1) were measured using microsphere-based immunoassay analysis. Differences between pretreatment and posttreatment tear samples were analyzed using the Wilcoxon test. RESULTS: No significant differences in ophthalmic symptoms or cytokine levels were observed between responders and nonresponders at baseline. After 1 month of topical treatment, ocular surface parameters (including Ocular Surface Disease Index, National Institutes of Health eye score, best-corrected visual acuity, corneal fluorescein staining score, and fluorescein tear film break-up time) were significantly ameliorated in responders, but not in nonresponders. Moreover, none of the cytokines exhibited significant alteration in nonresponders, whereas the tear levels of IL-6 (P = 0.031) and IL-8 (P = 0.037) exhibited significant decreases in responding patients. CONCLUSIONS: Our results revealed that tear IL-6 and IL-8 levels were significantly altered in response to topical oGVHD treatment.

Axenfeld-Rieger syndrome: a novel histopathologic finding associated with corneal abnormalities.

BACKGROUND: Axenfeld-Rieger syndrome (ARS) is a rare kind of anterior segment dysgenesis (ASD). The most common ocular features of ARS are posterior embryotoxon and iris hypoplasia, while some patients may manifest as corneal opacity and edema. However, the current understanding of how ARS affects the cornea is still incomplete. This study reports a novel histopathological finding of ARS, complicating corneal abnormalities, including congenital corneal opacity and irreversible endothelial decompensation. METHODS: This retrospective study included 6 eyes of 3 ARS patients, 5 of which underwent keratoplasty for irreversible endothelial decompensation from May 2016 to January 2019. No eye had a history of surgery. We reviewed the data of epidemiology, clinical manifestations and histopathologic examinations. RESULTS: Five eyes developed irreversible endothelial decompensation, among which 4 were born with corneal opacity. One eye exhibited transparent cornea but showed a continuous loss of endothelial cells in the absence of surgery and elevated intraocular pressure thereafter. Anterior segment optical coherence tomography photographs showed that anterior synechia existed in the area with corneal opacities, where we found the interlayer splitting of the Descemet membrane inserted by hypoplastic iris and a basement membrane-like structure under a light microscope. CONCLUSION: Anterior synechia might be associated with corneal abnormalities in ARS patients. The novel histopathologic finding revealed the internal relation between anterior segment dysgenesis and would help explore the inner mechanism of corneal abnormalities in ARS.

Biomarkers in Ocular Graft-Versus-Host Disease: Implications for the Involvement of B Cells.

Graft-versus-host disease (GVHD) is an immune-mediated inflammatory disease resulting from destruction of host tissue by donor immunoreactive cells and occurs in 30% to 70% of post-hematopoietic stem cell transplantation (HSCT) patients. Ocular involvement occurs in up to 60% to 90% of patients with chronic GVHD. T cells have long been recognized as a key driver of alloreactivity in chronic ocular GVHD (oGVHD). However, the role of B-cells has not been elucidated. To further explore the involvement of B-cells in the immune mechanism of chronic oGVHD and to uncover more sensitive biomarker indicators, we conducted this study on the tear cytokine analysis of chronic oGVHD. The study enrolled 18 patients (27 eyes) diagnosed with chronic oGVHD and 11 patients (22 eyes) diagnosed with dry eye disease (DED) as a control group. The microsphere-based immunoassay was used to determine 29 tear cytokines in both groups. Spearman's test was used to analyze the correlation between cytokine levels and different ophthalmic indexes (National Institutes of Health eye score, fluorescein tear film break-up time, corneal fluorescein staining, and Schirmer's test). Receiver operating characteristic curves were used to assess the predictive potential of the identified cytokines for chronic oGVHD. Twenty tear cytokine levels were elevated in patients with chronic oGVHD compared to those with DED (P < .05). Proliferation-inducing ligand (APRIL) and epidermal growth factor showed lower levels in patients with chronic oGVHD. Ultimately, IL-2, 6, and 8, ICAM-1 (CD54), E-selectin (CD62E), neuropilin-1, and B-cell activation factor (BAFF) levels had a strong correlation with ophthalmic indexes and an area under the curve (AUC) > 0.85. BAFF/APRIL exhibited superior diagnostic capabilities (AUC = 0.995; 95% confidence interval, 0.983-1.000). Our study identified IL-2, 6, 8, ICAM-1, CD62E, E-selectin, neuropilin-1, and BAFF as promising tear biomarkers that can indicate the severity of chronic oGVHD. Notably, APRIL/BAFF shows superior diagnostic capabilities, revealing that B cells may play an important role as immune substrates in chronic oGVHD. © 2023 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

The clinical outcomes of keratoplasty in irreversible corneal decompensation secondary to Axenfeld-Rieger syndrome.

PURPOSE: To evaluate the clinical outcomes of penetrating keratoplasty (PK) and Descemet's stripping automated endothelial keratoplasty (DSAEK) in eyes with irreversible corneal decompensation secondary to Axenfeld-Rieger syndrome (ARS). METHODS: In this retrospective case series, a total of four eyes undergoing PK and seven eyes undergoing DSAEK, including one eye requiring one repeat DSAEK, between 2014 and 2021 were enrolled. Postoperative complications, graft survival, glaucoma treatment before and after keratoplasty, visual outcomes, and endothelial cell density were recorded. RESULTS: The mean follow-up duration was 34.4 ± 16.8 months. Before keratoplasty, the mean BCVA was 2.0 ± 0.4 LogMAR, and the mean IOP was 21.7 ± 8.1 mmHg. A total of 63.6% of eyes (7/11) received glaucoma treatment, including five eyes with glaucoma surgeries. After keratoplasty, 27.3% of eyes (3/11) exhibited secondary graft failure. The mean BCVA reached a maximum of 0.7 ± 0.5 LogMAR at 8.9 ± 7.5 months, with no significant difference between the PK and DSAEK groups (P1 = 1.00, P2 = 0.12). Four eyes with previous glaucoma surgeries exhibited markedly high IOP. A total of 72.7% of eyes (8/11) required additional glaucoma treatments. The mean endothelial cell loss (ECL) rates at 1, 6, 12 and 24 months were 43%, 49%, 63% and 54%, respectively, with no significant difference between the PK and DSAEK groups (P1 = 0.64, P2 = 1.00, P3 = 0.57, and P4 = 0.44). CONCLUSION: Both PK and DSAEK can successfully treat corneal decompensation secondary to ARS, resulting in similar outcomes with regard to IOP control, BCVA and ECL. IOP control is essential for postoperative management, especially for eyes with previous glaucoma surgeries.

A Fully Automated Segmentation and Morphometric Parameter Estimation System for Assessing Corneal Endothelial Cell Images.

PURPOSE: To develop a fully automated segmentation and morphometric parameter estimation system for assessing corneal endothelial cells from in vivo confocal microscopy images. DESIGN: Artificial intelligence (neural network) study. METHODS: First, a fully automated deep learning system for assessing corneal endothelial cells was developed using the development set (from 99 subjects). Second, 184 images (from 97 subjects) were used to construct the testing set to evaluate the clinical validity and usefulness of the automated segmentation and morphometric system. Third, the automatically calculated endothelial cell density (ECD) values, Topcon's cell density, and manually calculated ECD were compared. RESULTS: After slit lamp examination, 88 healthy subjects, 2 Fuchs endothelial dystrophy patients, and 7 corneal endotheliitis patients were identified among the 97 subjects in the testing set. The automatedly estimated morphometric parameters for the testing set were an average number of 234 cells, an ECD of 2592 cells/mm2, a coefficient of variation in the cell area of 32.14%, and a percentage of hexagonal cells of 54.16%. Pearson's correlation coefficient between the automated ECD and Topcon's cell density and between the manually calculated ECD and Topcon's cell density was 0.932 (P < .01) and 0.818 (P < .01), respectively. The Bland-Altman plot of Topcon's cell density and the automated ECD yielded 95% limits of agreement between 271.94 and -572.46 (concordance correlation coefficient = 0.9). CONCLUSIONS: A fully automated method for segmenting corneal endothelial cells and estimating morphometric parameters using in vivo confocal microscopy images is more efficient and accurate for assessing the normal corneal endothelium.