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.

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.

Ophthalmic manifestations are associated with reduced tear lymphotoxin-α levels in chronic ocular graft-versus-host disease.

PURPOSE: To determine the role tear lymphotoxin-α (LT-α) in chronic ocular graft-versus-host disease (oGVHD). METHODS: Twenty-two chronic oGVHD and 17 control tear samples were collected, and commercial test strips were used to detect LT-α concentrations. Concentration differences between patients with and without oGVHD were determined via Mann-Whitney U test. The correlation between LT-α levels and ophthalmic parameters was analyzed using Spearman's test. RESULTS: The concentration of LT-α was significantly lower in oGVHD patients than in controls. LT-α levels were significantly correlated with OSDI, NIH eye score, T-BUT, and CFS among all participants. ROC analysis revealed that the area under the curve of LT-α was 0.847, and the cutoff value for chronic oGVHD diagnosis was 0.203 ng/mL. CONCLUSION: Our study revealed the significant decrease of tear LT-α in oGVHD, and suggested LT-α as a promising marker for chronic oGVHD diagnosis.

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.

Severe Corneal Edema Increases ECL From Grafts After DSAEK-Corneal Edema and ECL After DSAEK.

OBJECTIVES: To determine the relationship between the preoperative degree of corneal edema in the recipient and the endothelial cell density in grafts after Descemet stripping automated endothelial keratoplasty (DSAEK). METHODS: This retrospective case series enrolled 111 eyes of 107 patients who underwent DSAEK. The preoperative and postoperative central corneal thickness (CCT) was measured by anterior-segment optical coherence tomography. Eyes were divided into three groups according to the preoperative recipient CCT: group A (mild edema): 550 µm

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.

Evaluation of reconstructed human corneal endothelium sheets made with porcine Descemet's membrane in vitro and in vivo.

PURPOSE: To identify the feasibility of reconstructing corneal endothelial sheets by seeding non-infected monoclonal human corneal endothelial cells (HCECs) onto porcine Descemet's membrane (DM) and verifying the function in vitro and in vivo. METHODS: Denuded porcine DM was decellularized for haematoxylin and eosin staining, and DNA was removed via incubation with ethylene glycol diglycidyl ether (EGDE). The physical properties of the incubated DMs were evaluated and compared to those of unincubated DMs. The non-infected monoclonal HCECs were examined by chromosome analysis and the cell proliferation was evaluated by BrdU-labelling. Then HCECs at passage 30 were then seeded on the DM and cultured for approximately 5 days. The cell growth, density and expression of the sodium-potassium adenosine triphosphatase (Na+/K+-ATPase), the tight-junction-associated protein zonula occludens (ZO-1) and acetylated alpha tubulin were examined by electron microscopy and immunocytochemistry to compare HCECs cultivated on porcine DM and those cultured in vitro. Cells on the reconstructed HCEC sheets were labeled with DiI, and the sheets were subsequently transplanted into cat eyes via DM endothelial keratoplasty (DMEK). The corneal transparency, thickness, anterior segment, and HCEC density were monitored in vivo, and the corneal endothelial cell morphology and histological structure were examined ex vivo 98 days after surgery. RESULTS: No significant differences were observed in the elongation at break of the DMs and the thickness of the DMs incubated with EGDE compared to those of the unincubated DMs (P > 0.05). Results of chromosome analysis shown the number of the HCEC cell line was still 46 and no abnormal chromosome structure was found. BrdU-labelling shown the HCECs stopped proliferating after 5 days and the cells formed a single layer. The cells transferred to porcine DM formed tight connections with the substrate and generated layers of hexagonal cells on day 5. Adjacent cells cultivated on DM were closely attached to each other, tightly adhered to the porcine DM and expressed the Na+/K+-ATPase, ZO-1 protein and acetylated alpha tubulin, as did HCECs cultured in vitro. In addition, the HCEC density on DMs was 3020.14 ± 52.30 cells/mm2. After surgery, the corneas gradually became transparent, and the thickness decreased to 525.33 ± 56.23 µm at day 98 after the transplantation, while the control corneas showed consistent oedema during the monitoring period. The HCEC density was 2521.60 ± 78.24 cells/mm2 in vivo 98 days after transplantation. The histological results showed that the DiI-labeled cells were dense in the transplanted area and had a hexagonal or polygonal morphology and a normal ultrastructure; adjacent cells were closely attached to each other and tightly adhered to the porcine DM. CONCLUSIONS: Seeding non-infected monoclonal HCECs on porcine DM could reconstruct functional corneal endothelial sheets. These results may help uncover new applications for tissue-engineered endothelium in endothelial keratoplasty.

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.

Keratometric measurements and IOL calculations in pseudophakic post-DSAEK patients.

BACKGROUND: To compare different K readings in pseudophakic patients post-Descemet's stripping automated endothelial keratoplasty (DSAEK) and evaluate corresponding prediction errors in intraocular lens (IOL) power calculations. METHODS: Subjects that underwent cataract surgery and DSAEK surgery at least 3 and 6 months prior, respectively, and IOL implantation in the capsular bag were included in this study. Manifest refraction and IOL information were recorded. A Scheimpflug keratometer (Pentacam) was used for corneal measurements, including the mean anterior and posterior radii of curvature, simulated keratometer (SimK), true net power (TNP), and equivalent K reading (EKR) at the 4.0-mm zone. Conventional keratometry was acquired using the IOLMaster (KMaster). The four K measurements were evaluated for calculating the predicted refraction. RESULTS: The study included 20 eyes from 19 subjects. The ratio of the posterior to the anterior corneal radius was 74.1 ± 3.24%. Comparison of the four keratometric methods (KMaster, SimK, EKR, and TNP) revealed statistically significant differences among all the methods besides KMaster and SimK. Of the four IOL calculation methods(KMaster, SimK, EKR and TNP method),the arithmetic prediction error of the KMaster, SimK, and EKR methods featured nonsignificant differences from zero(p = 0.07, 0.19 and 0.84 respectively); the EKR method calculated the highest percentage of eyes with IOLs within the prediction error. CONCLUSIONS: IOL calculations in post-DSAEK eyes using KMaster, SimK, and EKR can yield small refractive errors after surgery. The EKR (4.0-mm diameter) method was found to be the most accurate.

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.

Mertk gene expression and photoreceptor outer segment phagocytosis by cultured rat bone marrow mesenchymal stem cells.

BACKGROUND: Bone marrow mesenchymal stem cells (BM-MSCs) are multipotential stem cells that have been used for a broad spectrum of indications. Several investigations have used BM-MSCs to promote photoreceptor survival and suggested that BM-MSCs are a potential source of cell replacement therapy for some forms of retinal degeneration. PURPOSE: To investigate the expression of the MER proto-oncogene, tyrosine kinase (Mertk), involved in the disruption of RPE phagocytosis and the onset of autosomal recessive retinitis pigmentosa in rat BM-MSCs and to compare phagocytosis of the photoreceptor outer segment (POS) by BM-MSCs and RPE cells in vitro. METHODS: MSCs were isolated from the bone marrow of Brown Norway rats. Reverse transcription-PCR (RT-PCR) and western blot analyses were used to examine the expression of Mertk. The phagocytized POS was detected with double fluorescent labeling, transmission electron microscopy, and scanning electron microscopy. RESULTS: Mertk expression did not differ among the first three passages of BM-MSCs. Mertk gene expression was greater in the BM-MSCs than the RPE cells. Mertk protein expression in the BM-MSCs was similar to that in the RPE cells in the primary passage and was greater than that in the RPE cells in the other two passages. BM-MSCs at the first three passages phagocytized the POS more strongly than the RPE cells. The process of BM-MSC phagocytosis was similar to that of the RPE cells. CONCLUSIONS: BM-MSCs may be an effective cell source for treating retinal degeneration in terms of phagocytosis of the POS.

[Post operation complications analysis and their treatment of Descemet's stripping automated endothelium keratoplasty].

OBJECTIVE: To summarize intra and post operation complications and their treatment of Descemet's Stripping Automated Endothelium Keratoplasty (DSAEK), and provide our experience for its development in China. METHODS: Retrospective case study. Forty-seven eyes of 42 patients underwent DSAEK performed by one surgeon. Indications include: Pseudophakic or aphakic Bullous Keratopathy, 27 eyes (57.4%); Fuchs Endothelial Dystrophy, 7 eyes (14.9%); endothelial decompensation post vitrectomy, 3 eyes (6.4%); iridocorneal endothelial syndrome (ICE), 3 eyes (6.4%); congenital glaucoma, 3 eyes (6.4%); graft failure post endothelial keratoplasty, 3 eyes (6.4%); endothelial decompensation after open ocular injury and intraocular foreign body, 1 eye (2.1%). Nineteen eyes underwent single DSAEK (40.4%); eight combined phacoemulsification and intraocular lens implantation (17.0%); eight combined anterior chamber IOL (AC-IOL) removal plus anterior segment vitrectomy and posterior chamber IOL (PC-IOL) implantation (17.0%); eight combined anterior segment vitrectomy and PC-IOL suspension (17.0%); two combined cataract extraction and anterior segment vitrectomy (4.3%); two failed in DSAEK and underwent penetrating keratoplasty (4.3%). RESULTS: Dislocation is the most common postoperative complications. Ten eyes underwent dislocation in 47 eyes (21.3%), which was solved by air and viscoelastic agent injection. High intraocular pressure happened in 12 eyes (25.5%), in 11 of which had a history of glaucoma and 1 with ICE. After drug treatment, ten patients had stable intraocular pressure and two patients underwent ciliary body photocoagulation surgery (1 case with anterior chamber intraocular lens, 1 case with ICE). Reactions happened in 2 cases (4.3%) patients, including 1 case with anterior chamber IOL (AC-IOL) rehabilitating after drug treatment and the other with Fuch's corneal endothelial dysfunction being regrafted. CONCLUSION: Dislocation is the most common complication after corneal endothelial keratoplasty, and air injection in anterior chamber is a common and effective method; High intraocular pressure is the second postoperative complication. Preoperative history of glaucoma is closely related to postoperative high intraocular pressure.

Outcomes of Donor Corneas of Different Thicknesses From Endothelial Keratoplasty in Deep Anterior Lamellar Keratoplasty for Keratoconus.

PURPOSE: To evaluate the outcomes of divided residual donor corneas obtained from endothelial keratoplasty in keratoconus with deep anterior lamellar keratoplasty (DALK). METHODS: In this retrospective, comparative, clinical study, 103 keratoconic eyes that underwent DALK were enrolled; 67 eyes received thin grafts from Descemet stripping automated endothelial keratoplasty, and 36 received thick grafts from Descemet membrane endothelial keratoplasty. Baseline and postoperative central corneal thickness (CCT), inferior corneal thickness, uncorrected distance visual acuity, corrected distance visual acuity, corneal astigmatism, mean keratometry, biomechanical properties, and complication rates were measured. RESULTS: Six months after transplantation, the group receiving thin grafts had a CCT of only 455.1 ± 43.0 µm, whereas that of the group receiving thick grafts was 546.7 ± 44.2 µm. Both CCT and inferior corneal thickness in the thin group were significantly lower than those in the thick group (measured with Pentacam at 36 months, P < 0.001) and remained throughout the 5-year follow-up period. Both procedures had comparable postoperative logarithm of the minimum angle of resolution UDVAs, logarithm of the minimum angle of resolution corrected distance visual acuity, astigmatism, and mean keratometry values (36 months; P = 0.335, 0.286, 0.680, and 0.365, respectively). Corneal biomechanical analysis revealed that the thin group had a significantly higher stiffness parameter at the first applanation than the thick group at the 2-year follow-up (P = 0.036) while other parameters were equivalent. CONCLUSIONS: The outcomes of keratoplasty with donor tissue are comparable regardless of the thickness of the graft, which suggests that transplantation with either type of the split corneal procedure for DALK in patients with keratoconus is feasible.

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.

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.

Pathological characteristics of the different stages of Acanthamoeba keratitis.

AIMS: To classify the clinical stages of Acanthamoeba keratitis (AK), and clarify the relationship between pathological changes and clinical features. METHODS AND RESULTS: Between January 2007 and May 2012, AK was diagnosed in 11 eyes by pathological examination and confocal laser scanning microscopy. Pathological investigation of all cornea samples from keratoplasty was done with periodic acid-Schiff and haematoxylin and eosin stains. AK clinical stage, pathological features and postoperative treatment were studied retrospectively. The 11 cases were classified into development stage, convalescence stage, or cicatricial stage. In the development stage, marked conjunctival hyperaemia, a corneal epithelial defect, obvious corneal infiltration and progressive inflammation were seen; pathological changes comprised abundant inflammatory cells and a rounded cyst in the oedematous stroma, as well as a very small amount of neovascularization. In the convalescence cases, moderate conjunctival hyperaemia, corneal disciform structures, repair of the corneal epithelial defect and abundant neovascularization were seen; pathological changes included significant tissue necrosis and a small, shrunken cyst in the stroma, as well as significant neovascularization. In the cicatricial stage, keratoleukoma was seen; pathological changes comprised a few inflammatory cells and shrunken cysts scattered in the stroma. There were no cases of recurrence. CONCLUSIONS: The pathological features of different clinical stages confirmed the new clinical classification of AK.

[Comparison of I Care rebound tonometer and Goldmann applanation tonometer after Descemet's stripping with automated endothelium keratoplasty].

OBJECTIVE: To evaluate the influence of corneal thickness (CT) on the intraocular pressure (IOP) measurements, the agreement of IOP readings with I Care rebound tonometer (RBT) and Goldmann applanation tonometer (GAT), and the agreement of central and peripheral IOP values obtained by RBT. METHODS: Thirty-seven eyes of 34 patients after Descemet's stripping with automated endothelium keratoplasty (DSAEK) underwent CT measurement using anterior segment OCT (AS-OCT) followed by IOP evaluation with the GAT at corneal center and with the RBT at corneal center and at 1 mm from the limbus in the nasal and temporal directions. The mean IOP measurement by the RBT and measurement by the GAT were analysed by paired t test. Pearson correlation analysis were performed to assess the correlations between the measurement and the influence of CT on IOP values. Agreement between the tonometers was calculated using the Bland-Altman method. RESULTS: IOP obtained by GAT was (16.2 ± 4.7) mm Hg (1 mm Hg = 0.133 kPa), and IOP obtained from central cornea, nasal cornea and temporal cornea by RBT were (16.0 ± 5.3) mm Hg, (17.4 ± 5.0) mm Hg and (17.1 ± 5.0) mm Hg, respectively. There was no statistical difference between the IOP on central cornea obtained by GAT and RBT (t = 0.77, P = 0.446), IOP on the peripheral cornea were higher than on central cornea by RBT (t = 3.24, 3.17, P = 0.003), and they were positively correlated (r = 0.869, 0.911, P < 0.05). The IOP readings showed positive relationship to CT values. Bland-Altman scatter plots showed reasonable inter-method agreement between each technique of IOP measurements. CONCLUSIONS: After DSAEK, the IOP readings obtained by RBT or GAT show positive relationship to CT values. There are reasonable agreements between each technique of IOP measurements. Considering the special advantages, RBT is an effective method to observe the IOP changes after DSAEK.

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.

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.