Glaucoma drainage device implantation and cyclophotocoagulation in the management of refractory glaucoma after Descemet-stripping automated endothelial keratoplasty.

AIM: To compare the surgical outcomes of glaucoma drainage device implantation (GDI) and trans-scleral neodymium:YAG cyclophotocoagulation (CPC) in the management of refractory glaucoma after Descemet-stripping automated endothelial keratoplasty (DSAEK). METHODS: This retrospective study on observational case series enrolled 29 patients who underwent DSAEK and posterior anti-glaucoma surgery (15 with GDI and 14 with CPC). The main outcome measures were intraocular pressure (IOP), glaucoma surgery success rate (defined as IOP of 6-21 mm Hg without additional anti-glaucoma operation), number of glaucoma medications, endothelial graft status, and best-corrected visual acuity (BCVA). RESULTS: The mean follow-up time was 34.1 and 21.0mo for DSAEK or glaucoma surgeries, both for the GDI and CPC groups. Both groups showed significant IOP reduction after glaucoma surgery. The GDI group presented a significantly higher success rate in IOP control than the CPC group (60% vs 21.4%, P=0.03). Both procedures significantly decreased the number of glaucoma medications (P=0.03). Forty percent and 57% of cases in the GDI and the CPC group, respectively, experienced endothelial graft failure during follow-up (P=0.36). Significantly worse BCVA after surgery was observed in the CPC group but not in the GDI group. CONCLUSION: Both GDI and CPC significantly decrease IOP in eyes with glaucoma after DSAEK. GDI is preferable to CPC in refractory glaucoma cases after DSAEK, as it manifests a significantly higher success rate for IOP control, similar endothelial graft failure rate, and relatively preserves BCVA than CPC.

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.

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.

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.

Loss of endothelial cells in viral DNA-positive grafts after keratoplasty: a 2-year follow-up study.

BACKGROUND: To compare endothelial loss between recipients who received viral DNA-positive grafts and controls 2 years after corneal transplantation. METHODS: We retrospectively analysed the clinical data and endothelial cell density of recipients of viral DNA-positive grafts and age-, sex-, aetiology- and operation-matched controls from April 2017 to July 2019 at the Peking University Third Hospital, Beijing, China. RESULTS: A total of 23/942 (2.44%) donor corneal buttons tested virus-positive by real-time PCR. A total of 27 recipients (except for 2 recipients) of viral DNA-positive grafts and 48 recipients of viral DNA-negative grafts were included in this study. Recipients of viral DNA-positive grafts had a higher endothelial cell (EC) loss rate post-penetrating keratoplasty and post-descemet stripping automated endothelial keratoplasty (p<0.05), but post-deep lamellar keratoplasty, the EC loss rate was similar to that of the controls. Recipients of herpes simplex virus-1-, cytomegalovirus- and varicella-zoster virus-positive grafts all had a higher EC loss rate than the controls during the 12- and 24-month follow-up periods (p<0.05). CONCLUSION: We inferred that viruses might be hidden in corneal grafts and mainly incubate in the corneal endothelium. Viral DNA-positive grafts do not need to be replaced immediately and can be followed up for a long time.

Characteristics of Corneal Endotheliitis among Different Viruses by in Vivo Confocal Microscopy.

Objectives: To explore the cellular morphological characteristics and changes in corneal endotheliitis among different viruses by in vivo confocal microscopy (IVCM).Methods: Corneal confocal images of 44 eyes of 44 patients with HSV, VZV, CMV and EBV corneal endotheliitis were studied retrospectively. Corneal confocal images of 44 normal eyes were used as controls.Results: The pathogens included cytomegalovirus (n = 20), herpes simplex virus (n = 8), varicella zoster virus (n = 10), and Epstein Barr virus (n = 6). There were no differences in the evaluated structures among the different viruses except for the lengths of the subbasal nerves and Langerhans cell densities. Deviations in endothelial cell layers were not significant among different viruses except for owl's eye morphology.Conclusion: ICVM can assist in diagnosing endotheliitis. The results demonstrate that changes in the cornea were not different among the various viruses except for owl's eye morphology, the lengths of the subbasal nerves and Langerhans cell densities.

The incidence and influence of the donor corneas positive for herpesviridae DNA in keratoplasty.

PURPOSE: We detected the DNA of herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), varicella-zoster virus (VZV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV) in donor corneas and assessed the clinical outcomes of recipients who received virus-positive grafts. METHOD: All donor corneas were analyzed for the presence of HSV-1, HSV-2, VZV, CMV, and EBV by real-time PCR from April 2017 to July 2019. The medical records of the transplant patients who received virus-positive grafts were reviewed. RESULT: Twenty-three (2.44%) donor cornea buttons tested positive for herpesviridae DNA. The positivity rates of HSV-1, CMV, VZV, and EBV were 0.74%, 0.85%, 0.64%, and 0.21%, respectively. CONCLUSION: We suggest that the corneas from donors who had cancer, donors who were inpatients, and donors who had immunodeficiency or who were on immunosuppressive therapy should be tested for herpesviridae DNA before transplantation. Finally, HSV-1 can be transmitted from graft to recipient, but that CMV cannot be transmitted according to our observations. The donor corneas found to be HSV-1-positive have to be discarded and not used for keratoplasty.

Clinical Evaluation of Intravitreal Injection of Ganciclovir in Refractory Corneal Endotheliitis.

Purpose: To evaluate the efficacy and safety of intravitreal ganciclovir (GCV) injection in refractory endotheliitis.Methods: Retrospectively recruited 25 eyes with endotheliitis, proved by clinical manifestations, positive PCR for viral DNA and responded poor to topical and systemic antiviral medications. All patients received additional continued intravitreal GCV injections.Results: Cytomegalovirus (CMV), varicella zoster virus (VZV), and herpes simplex virus (HSV) DNA were detected in 64.0%, 28.0%, and 8.0% of the eyes, respectively. Within 2 weeks after the last injection, 16/25 eyes recovered corneal clarity; active keratic precipitates (KPs) were eliminated in 21/25 eyes; intraocular pressure (IOP) was controlled in 12/15 eyes with elevated IOP on study entry. Best-corrected visual acuity increased at the last follow-up (p = 0.016). Clinical recurrence occurred in three patients. No complications were detected.Conclusions: CMV endotheliitis was the main type of refractory endotheliitis. Despite its invasive nature, intravitreal GCV injection appears to be an effective method for refractory endotheliitis.

Clinical Manifestations and Characteristics of In Vivo Confocal Microscopy in Varicella Zoster Virus-Related Corneal Endotheliitis.

Objective: To explore the clinical characteristics and in vivo confocal microscopic (IVCM) findings of varicella zoster virus (VZV)-related corneal endotheliitis.Methods: Retrospectively reviewed 20 eyes with corneal edema which were diagnosed by real-time polymerase chain reaction.Results: one had VZV infection. Three had epithelial lesions. Six had mydriasis. Four had loss of iris pigment. Keratic precipitates (KPs) were mixed. Subbasal nerves had disappeared in 12 eyes. Langerhans cells were observed in seven eyes. The deviations in endothelial cell layers consisted of guttate (n = 1), enlarged intercellular gaps (n = 11), infiltration of inflammatory cells (n = 8), loss of defined cell boundaries (n = 1) and anomalous nucleus (n = 9). The shape of KPs in IVCM included type I (n = 6), type III (n = 3) and type IV (n = 4).Conclusion: VZV-related corneal endotheliitis is remarkably difficult to detect clinically. Most cases have no typical skin lesions. The typical clinical feature is that of segmental iris atrophy and mixed KPs.

Clinical outcomes after Descemet's stripping endothelial keratoplasty using donor corneas from children younger than 3 years.

IMPORTANCE: There is limited literature on paediatric donors in endothelial keratoplasty. BACKGROUND: This study investigated the efficacy of and appropriate paediatric donor age for Descemet's stripping endothelial keratoplasty (DSEK). DESIGN: Retrospective and observational case series. PARTICIPANTS: Thirty-eight consecutive patients underwent DSEK with paediatric donor corneas. METHODS: The age of the donors ranged from 32 weeks gestation (premature neonate) to 3 years old. All donor consents were obtained from the parents. The causes of donor death included traffic accident, congenital heart disease and neonatal respiratory distress syndrome. MAIN OUTCOME MEASURES: The outcome measures included best-corrected visual acuity, endothelial cell loss and complications. RESULTS: Best-corrected visual acuity at last follow-up was >20/40 in 28 of 38 eyes (73.7%). The mean preoperative endothelial cell density of donor corneas was 4682 ± 520 cells/mm2 . The mean endothelial cell density of grafts was 3977 ± 556 cells/mm2 at 18 months postoperatively. Three lenticules from premature neonate donors exhibited severe contraction postoperatively. The edge of six lenticules from donors <1-year-old exhibited contraction in the early postoperative period and gradually flattened spontaneously. Graft detachment occurred in one patient. CONCLUSIONS AND RELEVANCE: DSEK with paediatric donor corneas can achieve good clinical outcomes. The corneal lenticules from 1- to 3-year- old donors are suitable for DSEK while those from donors <1-year-old are less suitable due to the possibility of severe postoperative graft contraction.

Appositional angle closure in Chinese with primary angle closure and primary angle closure glaucoma after laser peripheral iridotomy.

PURPOSE: To determine the prevalence of appositional angle closure (AAC) after laser peripheral iridotomy (LPI) in the eyes of Chinese patients with primary angle closure (PAC) and primary angle closure glaucoma (PACG) and to evaluate its pathogenesis by investigating anatomic characteristics. METHODS: This was a cross-sectional observational study. PAC and PACG subjects were consecutively enrolled after LPI. Ultrasound biomicroscopy (UBM) images, obtained in darkness, of each quadrant without peripheral anterior synechia (PAS) under gonioscopy were qualitatively assessed. Darkroom provocative test (DRPT) was also performed. RESULTS: A total of 134 eyes of 134 patients were enrolled. AAC was observed in ≥ 1 quadrant of UBM image in 85 subjects (63.4%). There were 116 randomly selected quadrants without PAS for 134 patients (86.6%). AAC existed in 38 quadrants (32.8%). Among these, plateau iris accounted for 44.7%, anteriorly inserted iris for 13.2%, thick iris for 13.2%, and anteriorly inserted iris combined with thick iris for 18.4% of the total. One hundred fifteen patients underwent DRPT and its positive rate of eyes with AAC ≥ 2 quadrants (37.5% [12 of 32 patients]) was significantly higher than those ≤ 1 quadrant (16.9% [14 of 83 patients]; P = 0.018). However, no significant differences were found between eyes with nonsynechia plateau iris ≥ 2 quadrants (36.4% [4 of 11 patients]) and those ≤ 1 quadrant (21.2% [22 of 104 patients]; P = 0.266). CONCLUSIONS: Approximately two-thirds of PAC and PACG eyes of Chinese patients after LPI had AAC. Plateau iris accounted for less than 50% of AAC. Other factors such as a thick peripheral iris and an anteriorly inserted iris also contributed to AAC. DRPT results suggested AAC might have more functional meaning than plateau iris.

Optic disc analysis with Heidelberg Retina Tomography III in glaucoma with unilateral visual field defects.

PURPOSE: To find the optic disc features of asymmetric primary open-angle glaucoma. METHODS: In this observational case-control study, 52 consecutive open-angle glaucoma patients with unilateral visual field defects participated. In each patient, an optic disc analysis using Heidelberg Retina Tomography III (HRT-III) was performed. Optic disc parameters of HRT-III of eyes with abnormal visual fields were compared with their fellow eyes with normal visual fields. RESULTS: The optic disc area of the eyes with abnormal visual fields (2.35 +/- 0.55 mm(2)) was larger than that of the fellow eyes with normal visual fields (2.25 +/- 0.43 mm(2)) (P = 0.03). Of the eyes with abnormal visual fields, 63.5% had a larger optic disc area than their fellow eyes with normal visual fields. In addition, in the eyes with abnormal visual fields, the cup areas were larger (P = 0.000001-0.02), whereas the rim and retinal nerve fiber layer thicknesses were thinner (P = 0.000002-0.036) than those of the fellow eyes with normal visual fields. CONCLUSIONS: The optic disc area of eyes with abnormal visual fields was larger than that of their fellow eyes with normal visual fields, suggesting that Chinese open-angle glaucoma patients with larger optic discs might be susceptible to glaucomatous optic damage.

Usefulness of frequency-doubling technology for perimetrically normal eyes of open-angle glaucoma patients with unilateral field loss.

PURPOSE: To determine whether frequency-doubling technology (FDT) perimetry detects visual field loss in perimetrically normal eyes of patients with open-angle glaucoma (OAG) and whether these visual field defects subsequently are detected by standard automated perimetry (SAP), and to explore the relating factors of the progression from abnormalities based on FDT to visual field loss based on SAP. DESIGN: Prospective cohort study. PARTICIPANTS: Sixty-eight OAG patients with unilateral field loss detected by SAP (Octopus, G2 program; Interzeig, Schlieren, Switzerland). METHODS: Perimetrically normal eyes of participants were examined with the FDT N-30 threshold program (Humphrey Instruments, Welch-Allyn, Skaneateles, NY). The visual field examination was followed by a series of SAP examinations administered over 3 years. MAIN OUTCOME MEASURES: The relationship between FDT and subsequent SAP results in perimetrically normal eyes was analyzed. Glaucomatous optic neuropathy (GON), visual field indices, intraocular pressure (IOP), and central corneal thickness (CCT) were compared between converters (eyes with subsequent SAP abnormality) and nonconverters within perimetrically normal eyes with abnormal FDT results. Finally, the SAP test points were matched to the abnormal FDT sectors. The relative risk (RR) of subsequent SAP abnormality corresponding to FDT abnormal sectors was calculated. RESULTS: Sixty perimetrically normal eyes of 60 participants had complete data and a qualifying follow-up. Baseline FDT results were abnormal in 65%. Of the eyes with abnormal FDT results, 51% developed abnormal SAP results after 4 to 27 months, whereas none of the eyes with normal FDT results developed abnormal SAP results (P<0.05). In perimetrically normal eyes with abnormal FDT results, converters had a greater cup-to-disc ratio, more eyes with GON, larger and deeper cups, and worse FDT mean deviation than nonconverters (P<0.05). The IOP and CCT did not differ between the 2 groups. The RR of subsequent SAP abnormality corresponding to abnormal FDT sectors was 5.38 (95% confidence interval, 3.61-8.04; P<0.05). CONCLUSIONS: In perimetrically normal eyes of OAG patients, FDT detected visual field loss in almost 2 of every 3 of these eyes and also predicted to some extent future visual field loss on SAP. Severity of glaucomatous neuropathy at baseline was related to conversion of abnormalities on FDT to visual field loss on SAP.