Three-Dimensional Ultrastructure of the Normal Rod Photoreceptor Synapse and Degenerative Changes Induced by Retinal Detachment.

The rod photoreceptor synapse is the first synapse of dim-light vision and one of the most complex in the mammalian CNS. The components of its unique structure, a presynaptic ribbon and a single synaptic invagination enclosing several postsynaptic processes, have been identified, but disagreements about their organization remain. Here, we have used EM tomography to generate high-resolution images of 3-D volumes of the rod synapse from the female domestic cat. We have resolved the synaptic ribbon as a single structure, with a single arciform density, indicating the presence of one long site of transmitter release. The organization of the postsynaptic processes, which has been difficult to resolve with past methods, appears as a tetrad arrangement of two horizontal cell and two rod bipolar cell processes. Retinal detachment severely disrupts this organization. After 7 d, EM tomography reveals withdrawal of rod bipolar dendrites from most spherules; fragmentation of synaptic ribbons, which lose their tight association with the presynaptic membrane; and loss of the highly branched telodendria of the horizontal cell axon terminals. After detachment, the hilus, the opening through which postsynaptic processes enter the invagination, enlarges, exposing the normally sequestered environment within the invagination to the extracellular space of the outer plexiform layer. Our use of EM tomography provides the most accurate description to date of the complex rod synapse and details changes it undergoes during outer segment degeneration. These changes would be expected to disrupt the flow of information in the rod pathway.SIGNIFICANCE STATEMENT Ribbon-type synapses transmit the first electrical signals of vision and hearing. Despite their crucial role in sensory physiology, the three-dimensional ultrastructure of these synapses, especially the complex organization of the rod photoreceptor synapse, is not well understood. We used EM tomography to obtain 3-D imaging at nanoscale resolution to help resolve the organization of rod synapses in normal and detached retinas. This approach has enabled us to show that in the normal retina a single ribbon and arciform density oppose a tetrad of postsynaptic processes. In addition, it enabled us to provide a 3-D perspective of the ultrastructural changes that occur in response to retinal detachment.

Developing and validating a clinlabomics-based machine-learning model for early detection of retinal detachment in patients with high myopia.

BACKGROUND: Retinal detachment (RD) is a vision-threatening disorder of significant severity. Individuals with high myopia (HM) face a 2 to 6 times higher risk of developing RD compared to non-myopes. The timely identification of high myopia-related retinal detachment (HMRD) is crucial for effective treatment and prevention of additional vision impairment. Consequently, our objective was to streamline and validate a machine-learning model based on clinical laboratory omics (clinlabomics) for the early detection of RD in HM patients. METHODS: We extracted clinlabomics data from the electronic health records for 24,440 HM and 5607 HMRD between 2015 and 2022. Lasso regression analysis assessed fifty-nine variables, excluding collinear variables (variance inflation factor > 10). Four models based on random forest, gradient boosting machine (GBM), generalized linear model, and Deep Learning Model were trained for HMRD diagnosis and employed for internal validation. An external test of the models was done. Three random data sets were further processed to validate the performance of the diagnostic model. The primary outcomes were the area under the receiver operating characteristic curve (AUC) and the area under the precision-recall curve (AUCPR) to diagnose HMRD. RESULTS: Nine variables were selected by all models. Given the AUC and AUCPR values across the different sets, the GBM model was chosen as the final diagnostic model. The GBM model had an AUC of 0.8550 (95%CI = 0.8322-0.8967) and an AUCPR of 0.5584 (95%CI = 0.5250-0.5879) in the training set. The AUC and AUCPR in the internal validation were 0.8405 (95%CI = 0.8060-0.8966) and 0.5355 (95%CI = 0.4988-0.5732). During the external test evaluation, it reached an AUC of 0.7579 (95%CI = 0.7340-0.7840) and an AUCPR of 0.5587 (95%CI = 0.5345-0.5880). A similar discriminative capacity was observed in the three random data sets. The GBM model was well-calibrated across all the sets. The GBM-RD model was implemented into a web application that provides risk prediction for HM individuals. CONCLUSION: GBM algorithms based on nine features successfully predicted the diagnosis of RD in patients with HM, which will help ophthalmologists to establish a preliminary diagnosis and to improve diagnostic accuracy in the clinic.

Retinal Tear and Retinal Detachment after Cataract Surgery in Eyes with a Previous History of Treated Phakic Retinal Tears.

PURPOSE: To investigate the incidence and outcomes of retinal tear (RT) and retinal detachment (RD) after cataract extraction in patients with a history of previous phakic RT. DESIGN: Retrospective case series. PARTICIPANTS: Patients with phakic eyes with RT that were treated successfully with laser photocoagulation or cryotherapy and subsequently underwent cataract surgery. METHODS: A retrospective review of data between April 1, 2012, and May 31, 2023, was performed. Exclusions included prior vitreoretinal surgery before cataract removal and follow-up of less than 6 months after cataract surgery. MAIN OUTCOME MEASURES: The incidence of RTs and RDs after cataract surgery, along with visual and anatomic outcomes. RESULTS: Of 12 109 phakic eyes treated for RTs, 1039 eyes (8.6%) underwent cataract surgery. After exclusions, 713 eyes of 660 patients were studied. The mean ± standard deviation follow-up period after cataract surgery was 34.8 ± 24.6 months, with a median of 239 and 246 days to a new RT or RD development, respectively. The overall incidence of RT and RD diagnosis after cataract surgery was 7.3% (52/713; 2.9% and 4.3%, respectively), with a 1-year incidence of 5.6% (2.2% and 3.4%, respectively). Multivariable regression analysis identified a higher risk of RT and RD among younger individuals (odds ratio [OR], 1.034; P = 0.028), male patients (OR, 2.058; P = 0.022), and those with a shorter interval between laser treatment and cataract surgery (OR, 1.001; P = 0.011). Single-surgery anatomic success for the RD repair was achieved in 25 eyes (80.6%) at 3 months, with a 100% final reattachment rate. The median final visual acuity was 0.10 logarithm of the minimum angle of resolution (logMAR; Snellen equivalent, 20/25) for RT, showing no significant change from after cataract surgery, and 0.18 logMAR (Snellen equivalent, 20/30) for RD, a significant worsening from after cataract surgery. CONCLUSIONS: One year after cataract surgery, the rate of diagnosed RT and RD in patients with previously treated RTs was relatively high, occurring in nearly 1 in 18 eyes. Higher risk was noted among younger individuals, male patients, and patients with a shorter interval between initial treatment for RT and cataract surgery. Retinal detachment repair achieved good anatomic results, but vision declined. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Association of Cutaneous Keloids, Hypertrophic Scarring, and Fibrosis with Risk of Postoperative Proliferative Vitreoretinopathy.

PURPOSE: To assess an association between cutaneous keloids, hypertrophic scarring, and fibrosis (KHF) and risk of postoperative proliferative vitreoretinopathy (PVR) after rhegmatogenous retinal detachment (RRD) repair. DESIGN: Retrospective, population-based cohort study. PARTICIPANTS: Patients aged ≥ 18 years who underwent initial retinal detachment (RD) repair with pars plana vitrectomy with or without scleral buckle (SB) (Current Procedural Terminology [CPT] 67108), pneumatic retinopexy (67110), and primary SB (67107) from January 1, 2003, to March 1, 2023. METHODS: A de-identified electronic health record database through TriNetX, a global health research network, was used to analyze patients. Patients were queried for International Classification of Diseases, 10th Revision (ICD-10) codes L91.0 (hypertrophic scar) and L90.5 (scar conditions and fibrosis of skin). Frequency of subsequent diagnosis of PVR (H35.2) and CPT codes for secondary surgery including complex RD repair (67113) were determined. Patients with proliferative diabetic retinopathy (PDR) (ICD-10 H10.35/H11.35) were excluded. Descriptive statistics (Z-test) and propensity score matching (PSM) were used to match for age, sex, and race. MAIN OUTCOME MEASURES: Prevalence of H35.2 and CPT 67113 within 180 days after RRD repair in the KHF cohort versus the non-KHF cohort. RESULTS: Among patients with CPT 67108, 1061 in each cohort (KHF and non-KHF) were analyzed after PSM. The mean (standard deviation) age was 60.7 (15.2) years. Within 180 days, 10.1% of patients in the KHF cohort and 3.4% in the non-KHF cohort had a diagnosis of PVR (H35.2) (P < 0.001, odds ratio [OR], 3.2; 95% confidence interval [CI], 2.13-4.71). A total of 8.3% of patients in the KHF cohort and 5.4% of patients in the non-KHF cohort underwent complex RD repair (CPT 67113) (P = 0.008; OR, 3.2; 95% CI, 1.13-2.25). When including all RD repair types (CPT 67108, 67110, 67107), the rate of PVR diagnosis was still significantly greater in the KHF cohort than in the non-KHF cohort (9.0% vs 4.2%, P < 0.01; OR, 2.28; 95% CI, 1.64-3.16). CONCLUSIONS: A dermatologic history of KHF may be a risk factor for PVR after RD repair. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Improved Outcomes with Heavy Silicone Oil in Complex Primary Retinal Detachment: A Large Multicenter Matched Cohort Study.

PURPOSE: To establish whether Densiron 68, a heavier-than-water endotamponade agent, is an effective alternative to conventional light silicone oil in primary rhegmatogenous retinal detachment (RD) surgery for eyes with inferior breaks in the detached retina and severe proliferative vitreoretinopathy (PVR). DESIGN: Cohort study of routinely collected data from the European Society of Retina Specialists and British and Eire Association of Vitreoretinal Surgeons vitreoretinal database between 2015 and 2022. PARTICIPANTS: All consecutive eyes that underwent primary rhegmatogenous RD surgery using Densiron 68 or light silicone oil as an internal tamponade agent. METHODS: To minimize confounding bias, we undertook 2:1 nearest-neighbor matching on inferior breaks, large inferior rhegmatogenous RDs, PVR, and, for visual analyses, baseline visual acuity (VA) between treatment groups. We fit regression models including prognostically relevant covariates, treatment-covariate interactions, and matching weights. We used g-computation with cluster-robust methods to estimate marginal effects. For nonlinear models, we calculated confidence intervals (CIs) using bias-corrected cluster bootstrapping with 9999 replications. MAIN OUTCOME MEASURES: Presence of a fully attached retina and VA at least 2 months after oil removal. RESULTS: Of 1061 eyes enrolled, 426 and 239 were included in our matched samples for anatomic and visual outcome analyses, respectively. The primary success rate was higher in the Densiron 68 group (113 of 142; 80%) compared with the light silicone oil group (180 of 284; 63%), with an adjusted odds ratio of 1.90 (95% CI, 1.63-2.23, P < 0.001). We also observed a significant improvement favoring Densiron 68 of -0.26 logarithm of the minimum angle of resolution (logMAR) in postoperative VA between the 2 groups (95% CI, -0.43 to -0.10, P = 0.002). The anatomic benefit of using Densiron 68 in eyes with inferior retinal breaks and large detachments was more pronounced among eyes with PVR grade C. We found no evidence of visual effect moderation by anatomic outcome or foveal attachment. CONCLUSIONS: Densiron achieved higher anatomic success rates and improved visual outcomes compared with conventional light silicone oil in eyes with inferior retinal pathology and severe PVR. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Ultra-Widefield-Guided Swept-Source OCT Findings of Peripheral Vitreoretinal Abnormality in Young Myopes.

PURPOSE: To evaluate the ultra-widefield fundus photography (UWF-FP)-guided swept-source OCT (SS-OCT) images of peripheral vitreoretinal abnormality (PVRA) in young asymptomatic myopes. DESIGN: Cross-sectional, single-center study. PARTICIPANTS: A total of 1966 eyes of 983 consecutive patients aged 18 to 42 years with refractive error in the spherical equivalent of < 0 diopters (D) who visited KEYE Eye Center, Seoul, Republic of Korea, for refractive surgery. METHODS: The prevalence of PVRA and their characteristics, including shape, location, presence of pigmentation, membrane, retinal breaks, and detachment, were evaluated. A logistic regression analysis was done to evaluate the risk factors of PVRA and the risk of retinal breaks or detachment among eyes with PVRA. RESULTS: Among 1966 eyes, 317 (16.1%) had PVRA, and 182 (57.4%) and 135 (42.6%) had focal and linear lesions, respectively. The risk of PVRA was increased with axial length of the eyes (odds ratio [OR], 1.238, 95% confidence interval [CI], 1.112-1.379, P < 0.001), corneal astigmatism (OR, 1.320, 95% CI, 1.148-1.519, P < 0.001), presence of discrete margins of different retinal reflectivity (DMDRR; indicating outer retinal disruption from abnormal vitreoretinal traction) (OR, 1.751, 95% CI, 1.334-2.300, P < 0.001), and posterior vitreous detachment (PVD) at the posterior pole of the retina (OR, 1.833, 95% CI, 1.352-2.485, P < 0.001). Among eyes with PVRA, patient age (OR, 1.063, 95% CI, 1.008-1.121, P = 0.025), linear lesions (OR, 15.234, 95% CI, 7.891-29.407, P < 0.001), and multiple lesions (OR, 3.432, 95% CI, 1.780-6.620, P < 0.001) were independently associated with the presence of retinal breaks or detachment. CONCLUSIONS: The follow-up for PVRA among young myopes should be personalized on the basis of their ocular characteristics, including asymmetric ocular expansion (axial length and astigmatism) and vitreoretinal interface status. The treatment plan for PVRA eyes should emphasize the greater risk of retinal breaks and detachment with increasing age and the presence of linear and multiple lesions. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

New kinase-deficient PAK2 variants associated with Knobloch syndrome type 2.

The p21-activated kinase (PAK) family of proteins regulates various processes requiring dynamic cytoskeleton organization such as cell adhesion, migration, proliferation, and apoptosis. Among the six members of the protein family, PAK2 is specifically involved in apoptosis, angiogenesis, or the development of endothelial cells. We report a novel de novo heterozygous missense PAK2 variant, p.(Thr406Met), found in a newborn with clinical manifestations of Knobloch syndrome. In vitro experiments indicated that this and another reported variant, p.(Asp425Asn), result in substantially impaired protein kinase activity. Similar findings were described previously for the PAK2 p.(Glu435Lys) variant found in two siblings with proposed Knobloch syndrome type 2 (KNO2). These new variants support the association of PAK2 kinase deficiency with a second, autosomal dominant form of Knobloch syndrome: KNO2.

Comprehensive exploration of hub genes involved in oxidative stress in rhegmatogenous retinal detachment based on bioinformatics analysis.

Rhegmatogenous retinal detachment (RRD) is a type of ophthalmologic emergency, if left untreated, the blindness rate approaches 100 %. The RRD patient postoperative recovery of visual function is unsatisfactory, most notably due to photoreceptor death. We conducted to identify the key genes for oxidative stress (OS) in RRD through bioinformatics analysis and clinical validation, thus providing new ideas for the recovery of visual function in RRD patients after surgery. A gene database for RRD was obtained from the Gene Expression Omnibus (GEO) database (GSE28133). Then we screened differentially expressed OS genes (DEOSGs) from the database and assessed the critical pathways in RRD with Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Protein-protein interaction (PPI) networks and hub genes among the common DEOSGs were identified. In addition, we collected general information and vitreous fluid from 42 patients with RRD and 22 controls [11 each of epiretinal membrane (EM) and macular hole (MH)], examined the expression levels of proteins encoded by hub genes in vitreous fluid by enzyme-linked immunosorbent assay (ELISA) to further assess the relationship between the ELISA data and the clinical characteristics of patients with RRD. Ten hub genes (CCL2, ICAM1, STAT3, CD4, ITGAM, PTPRC, CCL5, IL18, TLR2, VCAM1) were finally screened out from the dataset. The ELISA results showed that, compared with the control group, patients with RRD: TLR2 and ICAM-1 were significantly elevated, and CCL2 had a tendency to be elevated, but no statistically significant; RRD patients and MH patients compared with EM patients: STAT3 and VCAM-1 were significantly elevated. We found affected eyes of RRD patients compared with healthy eyes: temporal and nasal retinal nerve fiber layer (RNFL) were significantly thickened. By correlation analysis, we found that: STAT3 was negatively correlated with ocular perfusion pressure (OPP); temporal RNFL was not only significantly positively correlated with CCL2, but also negatively correlated with Scotopic b-wave amplitude. These findings help us to further explore the mechanism of RRD development and provide new ideas for finding postoperative visual function recovery.

Ophthalmic manifestations of Czech dysplasia.

Czech dysplasia is an autosomal dominant type 2 collagenopathy that is caused by heterozygosity for the recurrent p.(Arg275Cys) COL2A1 variant. Affected individuals usually present with skeletal abnormalities such as metatarsal hypoplasia of the third and fourth toes and early-onset arthropathy, as well as hearing loss. To date, no ophthalmic findings have been reported in patients with Czech dysplasia even though COL2A1 has been implicated in other ocular conditions such as type 1 Stickler syndrome. For the first time, we report the ocular findings in four families with Czech dysplasia, including type 1 vitreous anomaly, hypoplastic vitreous, retinal tears, and significant refractive error. These novel ocular findings expand the phenotype associated with Czech dysplasia and may aid clinicians as an additional diagnostic feature. Patients with congenital abnormalities of vitreous gel architecture have an increased risk of retinal detachment, and as such, patients may benefit from prophylaxis. Considering that many of the patients did not report any ocular symptoms, vitreous phenotyping is of key importance in identifying the need for counseling with regard to prophylaxis.

Incidence and progression of diabetic retinopathy in patients treated with glucagon-like peptide-1 receptor agonists versus sodium-glucose cotransporter 2 inhibitors: A population-based cohort study.

AIM: Glucagon-like peptide 1 receptor agonists (GLP1RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) are both recommended for patients with diabetes, yet their effects on the development or progression of diabetic retinopathy (DR) are largely unknown. METHODS: In this retrospective cohort study, data were collected from a nationwide database. Patients with diabetes who initiated treatment with a GLP1RA or SGLT2i between 1 May 2016 and 31 December 2017, were identified. Patients were divided into those with or without a previous diagnosis of DR and then categorized into the GLP1RA and the SGLT2i groups according to drug use. The primary outcome of interest in the DR group was the composite of new-onset proliferative DR, vitreous haemorrhage and tractional retinal detachment (RD). In the non-DR group, the primary outcome was the composite of newly diagnosed DR of any severity, vitreous haemorrhage and RD. RESULTS: In total, 97 413 patients were identified. After matching, 1517 patients were treated with a GLP1RA and 3034 with an SGLT2i in the DR cohort. In the non-DR cohort, 9549 initiated a GLP1RA and 19 098 initiated an SGLT2i. In patients with pre-existing DR, the incidence of any DR progression event was significantly higher in the GLP1RA group than the SGLT2i group (subdistribution hazard ratio 1.50, 95% confidence interval 1.01-2.23), primarily because of the increased risk of tractional RD. In patients without DR at baseline, the risks of all ocular outcomes were similar between the GLP1RA and SGLT2i groups. CONCLUSIONS: In patients with diabetes mellitus and established DR, GLP1RA treatment was associated with increased risks of DR progression compared with SGLT2i use.

Characteristics and surgery outcomes of macular hole diagnosed after rhegmatogenous retinal detachment repair.

PURPOSE: To report the characteristics and the visual and anatomical outcomes of secondary macular holes (SMHs) diagnosed after rhegmatogenous retinal detachment (RRD) repair and their associated factors. METHODS: Retrospective, interventional case series. All consecutive patients who were diagnosed with SMH after RRD repair at Beijing Tongren eye center from January 2016 to April 2021 were included. Patients who had their primary RRD repair in other hospitals and were referred to our center after diagnosis of SMH were also included. The minimum follow-up time after RRD repair was 6 months. RESULTS: 37 SMHs were diagnosed within a series of 5696 RRDs. Including 24 eyes referred from other hospitals after the diagnosis of SMH, 61 eyes were included. The type of primary RRD repair surgery included 22/61 (36%) eyes with scleral buckling procedure (SBP) and 39/61 (64%) eyes with pars plana vitrectomy (PPV). 21/61 (34%) eyes had recurrent RD. The median time to SMH diagnosis was 150 days (range, 7 ~ 4380 days). Macular hole (MH) closure was achieved in 77% eyes. Visual acuity (VA) improvement of at least 2 lines of Snellen's visual acuity was observed in 51% eyes. Final MH closure status was associated with preoperative MH diameter (for every 50 µm increment) (P = 0.046, OR = 0.875, 95%CI: 0.767 ~ 0.998). VA improvement was associated with final MH closure status (P = 0.009, OR = 8.742, 95%CI: 1.711 ~ 44.672). Final VA (logMAR) was associated with recurrent RD (P < 0.001, B = 0.663, 95%CI: 0.390 ~ 0.935), preoperative MH diameter (P = 0.001, B = 0.038, 95%CI: 0.017 ~ 0.058), VA at the time of SMH diagnosis (P < 0.001, B = 0.783, 95%CI: 0.557 ~ 1.009) and final MH closure status (P = 0.024, B = -0.345, 95%CI: -0.644 ~ -0.046). For patients without recurrent RD, VA improvement and final VA was associated with final MH closure status (P = 0.016 and P < 0.001, respectively), while for patients with recurrent RD, VA improvement or final VA did not associate with final MH closure status (P > 0.05). CONCLUSION: For SMH diagnosed after RRD repair, final MH closure status was associated with preoperative MH diameter. Recurrent RD, larger preoperative MH diameter, worse VA at the time of SMH diagnosis and failed MH closure are predictive factors for worse final VA. Visual outcome is associated with final MH closure status in patients without recurrent RD, but not as so in patients with recurrent RD.

Risk factors for early and late retinal detachment after boston type I keratoprosthesis surgery.

PURPOSE: To determine the differential risk factors for retinal detachment (RD) after Boston Type 1 Keratoprosthesis (B1KPro) during the first year after surgery (early RD; ERD) and afterwards (late RD; LRD). METHODS: Retrospective cohort study of 94 eyes (90 patients) undergoing B1KPro implantation at Centro de Oftalmología Barraquer from June 2006 to July 2022 with a minimum follow-up of one year. RESULTS: The incidence of RD in the whole sample after B1KPro implantation was 29% (27/94), occurring in 21% of eyes (ERD; 20/94) the first year, and in 7% afterwards (LRD; 7/94). Hypotony was revealed as a significant risk factor for ERD (16/19 = 84%; OR = 14.5, P < 0.0001), together with aphakia (16/20 = 80%; OR = 5.9, P = 0.004), intraocular lens (IOL) removal (4/8 = 50%; OR = 6.2, P = 0.03), previous choroidal detachment (CD; 7/20 = 35%; OR = 35.5, P = 0.001) and previous pars plana vitrectomy (PPV; 15/20 = 75%; OR = 6.6, P = 0.006). Multivariate analysis included hypotony and PPV at any time as variables significantly associated with ERD occurrence. The occurrence of LRD was significantly related to peripheral retinal changes, detected few days before (4/6 = 66%; OR = 65, P < 0.0001). CONCLUSION: Hypotony emerged as one of the main factors influencing ERD occurrence after B1KPro implantation. Additionally, previous CD, PPV, aphakia, and IOL removal should be considered to estimate the risk of postoperative retinal detachment. In contrast, peripheral retinal changes after B1KPro seem to be significantly related to LRD occurrence. This study reinforces the need for frequent intraocular pressure evaluation, and comprehensive periodic retinal assessment over time. KEY MESSAGES: What is known Retinal detachment (RD) is a severe complication after Boston Type 1 Keratoprosthesis (B1KPro) implantation, resulting in a permanent reduction of visual acuity in a clinically relevant percentage of eyes. The time of RD occurrence after B1KPro implantation differs in the literature but is reported to be more common within the first year. Previous aphakia, choroidal detachment, or RD repair, intraocular lens removal, vitritis, or history of Nd-YAG laser have been described as risk factors for RD after B1KPro surgery in samples with varying follow-ups. WHAT IS NEW: Multivariate analysis in the first year after B1KPro surgery showed hypotony and pars plana vitrectomy at any time as significant risk factors for early RD. Late RD cases, occurring after one year following the B1KPro surgery, seem to be significantly related to peripheral retinal changes suffered a few days before loss of visual acuity and RD diagnosis. It is plausible to think that risk factors for RD after B1KPro differ in short and long postoperative times.

The rising tide of rhegmatogenous retinal detachment in Germany: a nationwide analysis of the incidence, from 2005 to 2021.

PURPOSE: This nationwide study aims to delineate the incidence and trends of rhegmatogenous retinal detachment (rRD) in Germany across 17 years (2005-2021). METHODS: We conducted a retrospective cohort study using data from the German Federal Statistics Office and the Institute for the Hospital Remuneration System (InEK). The dataset includes approximately 19 million annual inpatient admissions annually. Retinal detachment was identified through ICD-10 code H33.0. Adjusted incidence rates were estimated after excluding reoperation cases. We used R Statistical Software to calculate estimates to 2021, and Tableau for visualisation. RESULTS: From 2005 to 2021, Germany reported 332,650 rRD cases, with males consistently more affected. Adjusted incidence rose from 15.6 per 100,000 in 2005 to 24.8 in 2021. Variable annual percentage changes in incidence were noted, averaging 4.0% for males and 2.6% for females. The annual mean age of affected individuals ranged from 60.2 to 62 years, with a median age between 62 and 63, suggesting increasing diagnoses at younger ages. Hospital stays declined from 6 to 3.3 days, and higher management rates were observed in Saarland and Rhineland-Palatine. CONCLUSION: The study confirms an increasing incidence of rRD in Germany from 2005 to 2021, particularly among males. These findings call for further research to investigate the underlying causes. Collaboration among healthcare professionals, researchers, and policymakers is essential for effective management and improved visual outcomes.

Retinal detachment and mortality in patients with cytomegalovirus retinitis: A multicenter study in taiwan.

PURPOSE: To characterize patients with cytomegalovirus (CMV) retinitis and identify risk factors for retinal detachment (RD) and mortality in this Taiwanese patient population. METHODS: This retrospective study included patients diagnosed with CMV retinitis between 2007 and 2019. The diagnosis was confirmed through aqueous polymerase chain reaction (PCR). Relevant data were collected from the Chang Gung Research Database. Univariate Cox regression was performed to identify the associations of RD and mortality risks with various patient characteristics, including demographic features, comorbidities, laboratory results, and medication use patterns. RESULTS: In total, 32 patients with CMV retinitis were included. Among these patients, 78.1% had an immunocompromised status, including 56.3% with high-dose systemic steroid use, 21.9% with HIV infection, 12.5% with hematologic malignancy, and 9.4% with renal transplantation. Approximately 21.9% of patients had RD 2.4 ± 2.1 months after CMV retinitis diagnosis, and 34.4% died within 6.2 [4.2, 38.2] months after diagnosis. Patients with RD had a statistically significant, but likely not clinically significant, later initiation of anti-CMV medications compared to their non-RD counterparts (8 [5, 23] days vs. 2 [1, 11] days, p = 0.039). Mortality was significantly associated with older age (hazard ratio [HR]: 1.06; 95% confidence interval [CI]: 1.02-1.10), hematologic malignancy (HR: 5.92; 95% CI: 1.44-24.37), and positivity for CMV on blood PCR (HR: 4.93; 95% CI: 1.49-16.35). CONCLUSION: Our study suggests that older age, hematologic malignancy, and positivity for CMV on blood PCR are risk factors for mortality in patients with CMV retinitis. KEY MESSAGES: What is known Cytomegalovirus (CMV) retinitis is the predominant sight-threatening opportunistic ocular infection in patients with acquired immunodeficiency syndrome (AIDS). What is new In the era of highly active antiretroviral therapy for AIDS, the majority of CMV retinitis patients are those receiving immunomodulatory therapy for underlying diseases. Older age, hematologic malignancy, and positive blood polymerase chain reaction for CMV are potential risk factors for mortality in patients with CMV retinitis.

Intravitreal methotrexate as an adjuvant in vitrectomy in cases of retinal detachment with proliferative vitreoretinopathy.

PURPOSE: To compare the rate of re-detachment in patients with rhegmatogenous retinal detachment and Grade-C PVR following vitreoretinal surgery, with and without serial intravitreal injections of methotrexate. METHODS: It was a randomized control trial. Patients aged more than 18 years undergoing pars plana vitrectomy for rhegmatogenous retinal detachment with PVR grade C or more were included in the study. Patients treated with intravitreal injection of methotrexate were grouped as cases and those not injected served as controls. The cases received 3 intravitreal injections of methotrexate at monthly intervals. Patients were evaluated on Day 1, 1st month, 2nd month, 3rd month and 6th month in terms of BCVA, rate of re-attachment and grade of PVR. RESULTS: The case group had 23 patients and the control group had 20 patients. 2 patients in the case group were lost to follow-up after the first follow-up, so they were excluded. So 21 patients in case group and 20 patients in control group were followed up. Six months after surgery, 15 'cases' had completely attached retina whereas 6 patients had partial detachment with macula on. There was no patient amongst the cases with macula-off retinal re-detachment. Out of 20 patients in the control group, 9 had a complete retinal attachment, 4 had partial detachment with macula-on and 7 had partial detachment with macula-off. There was statistically significant difference in macula off retinal detachment rates (p-value- 0.003). CONCLUSION: Serial intravitreal methotrexate injections reduce the incidence of re-detachment in patients undergoing PPV for RRD with PVR-C. Further investigation into this promising therapeutic approach is warranted. KEY MESSAGES: What is known Methotrexate is an anti-inflammatory agent which is safe for intravitreal use There are case series retrospective and prospective studies suggesting potential benefit of intravitreal methotrexate in preventing re-detachment due to PVR What is new First randomized control trial studying the efficacy of intravitreal methotrexate in preventing re-detachment due to PVR Our study showed statistically significant difference in macula off retinal detachment between the 2 groups at 6 months of follow up.

Long-term efficacy and complications of intravitreal anti-vascular endothelial growth factor agents combined with ablative therapies in juvenile Coats disease: a five year follow-up study.

PURPOSE: To evaluate the long-term safety and efficacy of adjuvant intravitreal anti-VEGF therapy in juvenile Coats disease. METHODS: This retrospective, observational study included a total of 62 eyes in 62 pediatric patients with juvenile Coats disease treated with intravitreal anti-VEGF agents followed for a mean of 67.08 months (ranged from 60 to 93 months). All affected eyes were managed initially with one session of ablative treatment plus adjuvant intravitreal anti-VEGF agent (0.5 mg/0.05 ml ranibizumab or conbercept). Ablative treatment was repeated if telangiectatic retinal vessels were not completely regressed or recurred. Anti-VEGF therapy was repeated if subretinal fluid or macular edema still existed. Treatments above were repeated every 2 to 3 months. We reviewed clinical and photographic records of patients including the demographics, clinical characteristics and interventions. RESULTS: At final visit, all 62 affected eyes had partially or completely disease resolution; none progressed to advanced stage namely neovascular glaucoma or phthisis bulbi, respectively. No ocular or systemic side effects related to intravitreal injections were observed during follow-up. In terms of 42 affected eyes that could cooperate with visual examination, best corrected visual acuity improved in 14 (14/42, 33.3%) eyes, stabled in 25 (25/42, 59.5%) eyes, and worsened in 3 (3/42, 7.1%) eyes. In the field of complications, 22 (22/62, 35.5%) eyes developed cataracts; 33 (33/62, 53.2%) eyes developed vitreoretinal fibrosis, of whom 14 (14/33, 42.4%) eyes in the subgroup of stage 3B developed progressive TRD; 40 (40/62, 64.5%) eyes developed subretinal fibrosis. Multivariate regression analysis showed increased clinical stage may be associated with the development of vitreo- and subretinal fibrosis (adjusted odds ratio:16.77,17.59; 95% CI:4.50-62.53, 3.98-77.86, respectively, all P < 0.001). CONCLUSION: Adjuvant intravitreal ranibizumab or conbercept combined with ablative therapies may be a long-term safe and effective treatment for juvenile Coats disease.

Invivo generated autologous plasmin enzyme assisted vitrectomy, partial circumferential-oral retinotomy, silicone oil injection in patients with chronic retinal detachment without posterior vitreous detachment.

PURPOSE: To report the results of invivo generated autologous plasmin enzyme(IVAP) assisted vitrectomy, partial circumferential-oral retinotomy and silicone oil injection for surgical treatment of patients with chronic retinal detachment without posterior vitreous detachment(PVD). METHODS: Study was performed in retrospective, comparative manner. A total of 16 consecutive eyes with chronic retinal detachment who had intravitreal injection of 50 µgr of t-PA and 0.1 ml of autologous whole blood, 3 days before surgery, underwent lens extraction with phacoemulsification, IVAP assisted vitrectomy, partial circumferential-oral retinotomy, and silicone oil injection(Study Group) were compared to a similar group of 15 eyes who had undergone vitrectomy, with or without lens extraction and silicone oil injection(Control Group) for the treatment of chronic retinal detachment. Primary outcome measures were initial retinal reattachment and number of operations at postoperative 6 months. RESULTS: Mean age of 16 patients of whom 7 were female, was 39.31 ± 17.76 years in study group and 15 patients of whom 4 were female, was 35.40 ± 11.92 years (p = 0.607). Mean follow-up time was 10.68 ± 7.15 months in study group and 29.13 ± 18.83 months in control group (p = 0.001). Initial retinal reattachment was achieved in 87.50% (14 out of 16 patients) in the study group, whereas it was 46.66% (7 out of 15 patients) in the control group (p = 0.017). The mean number of operations for reattachment in the study group was 1.12 ± 0.34, whereas it was 1.46 ± 0.51 in the control group (p = 0.039) at postoperative 6 months While the preoperative LogMAR visual acuity was 1.25 ± 0.64, it was 0.53 ± 0.37 at postoperative 6 months in study group (p = 0.001). Conversely, in the control group, the preoperative LogMAR visual acuity was 1.22 ± 0.33, it was 1.20 ± 0.89 at postoperative 6 months (p = 0.780). At postoperative 6 months,, epiretinal membrane developed in 2 eyes of the study group, 1 eye in the control group, and phthisis bulbi occurred in 1 eye of control group. CONCLUSION: IVAP assisted vitrectomy, partial circumferential-oral retinotomy and silicone oil injection is effective and safe for the surgical treatment of chronic retinal detachment without PVD.

Optical coherence tomography homography for detection of retinal displacement: a validation study.

PURPOSE: Retinal displacement following rhegmatogenous retinal detachment (RRD) has been associated with inferior functional outcomes. Recent evidence using an overlay technique suggests that fundus-autofluorescence underestimates post-RRD repair retinal displacement. This study aims to validate the overlay technique in normal eyes and to determine its sensitivity and specificity at detecting retinal displacement. METHODS: We conducted a retrospective case series involving 66 normal eyes, each with at least two separate infrared (IR) images at different time points. Overlay of the two images was based on manual marking of choroidal and optic nerve head (ONH) landmarks. For each set of two IR images, computer code for homography generated two outputs, flipping view video and an overlay picture. First, validation of choroidal/ONH alignment was performed using the flipping view video to ensure accurate manual markings. Then, two different masked graders (AB + IM) evaluated the overlays for presence of retinal displacement. 16 control eyes following RRD repair with detected retinal displacement on FAF imaging assessed sensitivity and specificity of the technique. RESULTS: 94% of overlays were found to be well aligned (62/66). 11 cases exhibited errors on flipping view analysis (choroidal/ONH misalignment). Those 11 cases had a significantly higher rate of retinal displacement (false positives) compared to cases without errors (8/11,72% Vs 54/55,98%,P = 0.001). Sensitivity and specificity of the overlay technique for detecting retinal displacement considering only adequate flipping view cases (n = 55) were calculated as 100% and 98%, respectively. CONCLUSIONS: IR overlay emerges as a reliable and valid method for detecting retinal displacement, exhibiting excellent sensitivity and specificity.

Outcomes of rhegmatogenous retinal detachment surgery in patients with Stickler syndrome.

PURPOSE: Despite recent developments in vitrectomy technology and instrumentation, rhegmatogenous retinal detachment in Stickler syndrome (RDS) remains a challenge for surgeons. RDSs are associated with a higher rate of complications and surgical failures than those not associated with Stickler syndrome. This study is a report about anatomic and visual outcomes of RDS surgery and describes the surgical techniques associated with the treatment of this specific condition. METHODS: This is a retrospective, interventional, consecutive case series of patients with RDS undergoing retinal reattachment surgery from 1990 to 2020 at the Institute of Ocular Microsurgery (IMO) in Barcelona, Spain. RESULTS: Twenty-four eyes of 18 patients with genetically confirmed Stickler syndrome were included in the study. Ten eyes (41.6%) presented a giant retinal tear. Retinal reattachment was achieved in all cases after an average of 1.21 (range 1-6) surgical interventions. Nineteen eyes (79%) required only one operation to achieve complete retinal reattachment. The most common first surgical procedure was a 4-mm scleral buckle with posterior pars plana vitrectomy and silicone oil endotamponade, performed on 16 (66.6%) of the eyes. The mean follow-up period was 10.2 years. Mean preoperative visual acuity LogMar was 1.10 (Snellen equivalent 20/252), which improved to 0.50 (Snellen equivalent 20/63) at final follow-up (p < 0.05). CONCLUSION: In most RDS cases, anatomic success and visual acuity improvement can be achieved with the first surgical procedure, using a combination of silicone oil tamponade and a 4-mm scleral encircling band. In some early cases of RDS, other less invasive surgical techniques can be used.

Bilateral vitrectomy in patients with proliferative diabetic retinopathy-characteristics and surgical outcomes.

PURPOSE: Comparing characteristics and outcomes of patients with bilateral proliferative diabetic retinopathy (PDR) undergoing concurrent and sequential vitrectomy. METHODS: Patients having bilateral vitrectomy were classified into concurrent (requiring bilateral surgery simultaneously) and sequential (indicating vitrectomy in one eye later) groups. Clinical characteristics and outcomes were compared, and correlation between the first and second-operated eyes was analyzed. RESULTS: One hundred eight and 126 eyes were in the concurrent and sequential groups, respectively. The sequential group was older (50 vs. 45 years, P = 0.017), had less retinal detachment (54 vs. 77%, P < 0.001), and better visual outcomes (0.79 vs. 1.30, P = 0.021), especially the second-operated eyes. The concurrent group had weaker correlations of disease severity (phi coefficient: 0.36 vs. 0.61) and post-operative visual acuity (r: 0.12 vs. 0.34) between the first- and second-operated eyes than the sequential group. Prior intravitreal injection of anti-vascular endothelial growth factor (odds ratio [OR] 0.37, 95% confidence interval [CI] 0.15-0.86, P = 0.025) predicted better outcomes, while post-operative neovascular glaucoma predicted worse outcomes (OR 6.5, 95% CI 1.7-27.9, P = 0.008). CONCLUSIONS: PDR patients requiring surgery concurrently were younger and had more severe diseases and worse outcomes. However, poor outcomes in the first eye did not predict similar outcomes in the second eye.