360 DEGREE ENDOLASER VERSUS FOCAL ENDOLASER IN PRIMARY RHEGMATOGENOUS RETINAL DETACHMENT REPAIR.

PURPOSE: To determine the efficacy of the 360-degree endolaser (360EL) versus focal laser during primary vitrectomy (PPV) for rhegmatogenous retinal detachment (RRD) repair. METHODS: A single-site retrospective chart review was performed on 241 patients who underwent PPV for primary RRD. Patients were assigned to two groups, PPV with 360EL (n = 183) and PPV without 360EL (n = 59). Only cases where surgeons performed 360EL on all RRDs or surgeons who never perform 360EL on RRDs were included. RESULTS: The single surgery anatomical success rate in the 360EL group was 90.2% compared with 86.5% with focal laser ( P = 0.619). Epiretinal membrane formation in 360EL group at 1 year was 44.4% versus 37% with focal laser ( P = 0.429). Cystoid macular edema formation within 1 year of surgery was 25.8% in 360EL group versus 11.9% with focal laser ( P = 0.04). CONCLUSION: The use of 360EL in PPV for RRD repair does not improve single-surgery anatomical success in routine RRDs when compared with PPV with focal laser.

577-NM YELLOW LASER PHOTOCOAGULATION FOR COATS DISEASE.

PURPOSE: To describe the outcomes of children with Coats disease treated with 577-nm yellow laser indirect ophthalmoscopy. METHODS: A retrospective consecutive case series of pediatric patients with Coats disease treated at a single institution between 2011 and 2014. Laser indirect ophthalmoscopy was performed under anesthesia. Full treatment was defined as complete ablation of all visible telangiectasias and resolution of subretinal fluid. No patients were treated with cryotherapy or bevacizumab. RESULTS: Seventeen eyes of 16 patients were consecutively treated. At the time of diagnosis, the eye was classified as Stage 1 (telangiectasias only) in 1 case, Stage 2A (extra-foveal exudation) in 2 cases, Stage 2B (fovea-involving exudation) in 6 cases, Stage 3A1 (extra-foveal exudative retinal detachment) in 2 cases, Stage 3A2 (subtotal foveal-involving detachment) in 1 case, and Stage 3B (total exudative retinal detachment) in 5 cases. The mean age at initial treatment was 71.2 months. Mean length of follow-up was 20.8 months (median 18.5 months, range 3.7-37.3 months). Patients underwent an average of 2.5 laser treatments. Sixteen of 17 eyes achieved full treatment (94.1%) with a mean time-to-full-treatment of 11.2 months. One eye developed glaucoma and end-stage disease. CONCLUSION: 577-nm yellow wavelength laser indirect ophthalmoscopy is an effective treatment for Coats disease including cases of exudative retinal detachment.

Incidence of Akreos AO60 intraocular lens opacification after concurrent or subsequent intraocular oil or gas use.

PURPOSE: To report the incidence of opacification in a consecutive series of 10 eyes that underwent scleral fixated Akreos AO60 placement with concurrent or subsequent contact with gas or silicone oil. METHODS: Consecutive case series. RESULTS: Three cases of IOL opacification were noted. Two cases of opacification occurred in patients that underwent subsequent retinal detachment repair with C3F8 and one with silicone oil. One patient underwent explanation of the lens due to visually significant opacification. CONCLUSION: Scleral fixation of the Akreos AO60 IOL is associated with risk of IOL opacification when exposed to intraocular tamponade. While surgeons should consider the risk of opacification in patients at high risk of requiring intraocular tamponade, only 1 in 10 patients developed IOL opacification significant enough to require explantation.

N-cadherin and neuroligins cooperate to regulate synapse formation in hippocampal cultures.

Cadherins and neuroligins (NLs) represent two families of cell adhesion proteins that are essential for the establishment of synaptic connections in vitro; however, it remains unclear whether these proteins act in concert to regulate synapse density. Using a combination of overexpression and knockdown analyses in primary hippocampal neurons, we demonstrate that NL1 and N-cadherin promote the formation of glutamatergic synapses through a common functional pathway. Analysis of the spatial relationship between N-cadherin and NL1 indicates that in 14-day in vitro cultures, almost half of glutamatergic synapses are associated with both proteins, whereas only a subset of these synapses are associated with N-cadherin or NL1 alone. This suggests that NL1 and N-cadherin are spatially distributed in a manner that enables cooperation at synapses. In young cultures, N-cadherin clustering and its association with synaptic markers precede the clustering of NL1. Overexpression of N-cadherin at this time point enhances NL1 clustering and increases synapse density. Although N-cadherin is not sufficient to enhance NL1 clustering and synapse density in more mature cultures, knockdown of N-cadherin at later time points significantly attenuates the density of NL1 clusters and synapses. N-cadherin overexpression can partially rescue synapse loss in NL1 knockdown cells, possibly due to the ability of N-cadherin to recruit NL2 to glutamatergic synapses in these cells. We demonstrate that cadherins and NLs can act in concert to regulate synapse formation.

Characteristics of Pentosan Polysulfate Sodium-Associated Maculopathy and Similarities With Other Maculopathies Commonly Managed in a Retina Practice.

Purpose: This work describes characteristics of pentosan polysulfate sodium (PPS)-associated maculopathy and its similarities with common maculopathies in a retina practice cohort. Methods: Thirty-two patients were identified through electronic medical record query who were exposed to PPS. One patient was excluded for lack of retinal imaging. Thirty-one patients (62 eyes) were included. A retrospective review was used to obtain patient characteristics, examination findings, and retinal imaging of the study patients. Classification into "likely," "unlikely," or "possible" to have PPS-associated maculopathy groups was based on the fundus photography and retinal imaging. Main outcome measures were best-corrected visual acuity, age, sex, diagnosis of reason for referral, allocation into designated maculopathy group, and presence of choroidal neovascularization. Results: Of 31 patients (62 eyes), the median age was 70 years (range, 24-104 years) and the majority were women (87%). Mean best-corrected visual acuity was 0.3 ± 0.4 logMAR at presentation. The most common reason for referral was age-related macular degeneration (29%). Maculopathy grades were "likely" (29%, 9 total patients), "possible" (26%, 8 total patients), or "unlikely" (45%, 14 total patients). Choroidal neovascularization was noted in 9.7% of all eyes and 11% of eyes in the "likely" group. The "possible" and "likely" groups had older ages of presentation (P < .05) compared with the "unlikely" group. Conclusions: A high percentage (55%) of patients with a history of chronic PPS exposure showed features of "likely" or "possible" maculopathy. Similarities with common maculopathies such as age-related macular degeneration and the importance of screening and recognizing at-risk patients are highlighted.

Incidence of Delayed Vitreous Hemorrhage in Patients With Retinal Tears Associated With Bridging Vessels.

BACKGROUND AND OBJECTIVE: The purpose of this article is to determine if outcomes in patients presenting with retinal tears with bridging vessels (BVs) differ from those without BVs. PATIENTS AND METHODS: A case control study of all patients presenting with retinal tears during a 3-year period was completed. Comparisons were made between patients with and without BVs. Variables included vitreous hemorrhage (VH) at presentation, delayed VH, initial and final visual acuity, need for surgery, and retinal detachment. RESULTS: There was a significant increase in the number of patients with a VH at presentation (75% vs 28%; P < .0001), delayed VH (31% vs 7.5%; P = .001), and incidence of pars plana vitrectomy (16% vs 1.3%; P = .002) in the BV cohort. There was no significant difference in time to VH (9.4 vs 38.8 days; P = .32) or final visual acuity (20/25 vs 20/25; P = .45) between the two groups. CONCLUSIONS: The presence of a BV is an important prognostic indicator for risk of delayed VH. Documenting the presence of a BV allows for appropriate patient counseling. [Ophthalmic Surg Lasers Imaging Retina 2022;53:502-505.].

Describing Adverse Events Associated with Bilateral Same-Day Intravitreal Dexamethasone Implants.

BACKGROUND AND OBJECTIVES: To explore the incidence of adverse events after bilateral same-day intravitreal 0.7-mg dexamethasone implant (SDIDI) injections. MATERIALS AND METHODS: We performed an IRB approved, single-center, retrospective review of patients receiving bilateral SDIDI injections from January 1, 2016 to October 31, 2021 and reviewed adverse events that occurred within 3 months of injection. RESULTS: A total of 206 bilateral (412 eyes) SDIDI injections were performed in 59 patients. Ocular hypertension or the addition of intraocular pressure (IOP) lowering drops occurred in 121 (29.4%) eyes after IDI. Two (0.5%) eyes required glaucoma drainage surgeries. Of the 117 phakic eyes, 32 (27.4%) had progression of cataract or cataract extraction. There were two (0.5%) episodes of vitreous hemorrhage and one (0.2%) retinal tear with retinal detachment. There were no cases of endophthalmitis. CONCLUSION: Serious complication rates after bilateral same-day IDI injections appears low. Increased IOP that requires intervention can occur. [Ophthalmic Surg Lasers Imaging Retina 2022;53:612-618.].

A crystal-clear interaction: relating neuroligin/neurexin complex structure to function at the synapse.

Neuronal circuits are maintained by homeostatic mechanisms controlling synapse maturation and signaling. Neuroligins (NLs) and neurexins (Nrxs) may regulate the fine balance between excitation and inhibition. In this issue of Neuron, Araç et al. and Fabrichny et al. define crystal structures of NLs bound to beta-Nrx, providing insights into their synaptic actions and clarifying structural defects associated with autism-linked mutations.

Synaptic localization of neuroligin 2 in the rodent retina: comparative study with the dystroglycan-containing complex.

Several recent studies have shown that neuroligin 2 (NL2), a component of the cell adhesion neurexins-neuroligins complex, is localized postsynaptically at hippocampal and other inhibitory synapses throughout the brain. Other studies have shown that components of the dystroglycan complex are also localized at a subset of inhibitory synapses and are coexpressed with NL2 in brain. These data prompted us to undertake a comparative study between the localization of NL2 and the dystroglycan complex in the rodent retina. First, we determined that NL2 mRNA is expressed both in the inner and in the outer nuclear layers. Second, we found that NL2 is localized both in the inner and in the outer synaptic plexiform layers. In the latter, the horseshoe-shaped pattern of NL2 and its extensive colocalization with RIM2, a component of the presynaptic active zone at ribbon synapses, argue that NL2 is localized presynaptically at photoreceptor terminals. Third, comparison of NL2 and the dystroglycan complex distribution patterns reveals that, despite their coexpression in the outer plexiform layer, they are spatially segregated within distinct domains of the photoreceptor terminals, where NL2 is selectively associated with the active zone and the dystroglycan complex is distally distributed in the lateral regions. Finally, we report that the dystroglycan deficiency in the mdx(3cv) mouse does not alter NL2 localization in the outer plexiform layer. These data show that the NL2- and dystroglycan-containing complexes are differentially localized in the presynaptic photoreceptor terminals and suggest that they may serve distinct functions in retina.

Building excitatory and inhibitory synapses: balancing neuroligin partnerships.

Processing of neural information is thought to occur by integration of excitatory and inhibitory synaptic inputs. As such, precise control mechanisms must exist to maintain an appropriate balance between each synapse type. Recent findings indicate that neuroligins and their synaptic binding partners modulate the development of both excitatory and inhibitory synapses. Here we highlight these findings and discuss a mechanism potentially involved in controlling the balance between excitation and inhibition.

Timing of Povidone-Iodine Application to Reduce the Risk of Endophthalmitis after Intravitreal Injections.

PURPOSE: To analyze comparatively the effect of different intravitreal injection (IVI) protocols on the incidence of endophthalmitis occurring after injection. DESIGN: Retrospective case-control series. PARTICIPANTS: Twenty-seven retina specialists in a large vitreoretinal practice performed 37 646 IVIs. METHODS: Multivariate analysis was used to identify risk factors for development of endophthalmitis occurring after injection. Before all injections, a technician applied 5% povidone-iodine (PI) to the eyelids and conjunctiva. There were 4 distinct aseptic protocols with regard to reapplication of PI by physicians: physicians who did not reapply PI, reapplication of PI without the use of a lid speculum, reapplication of PI before speculum placement, and reapplication of PI after speculum placement. Other analyzed variables included the use of gloves, a caliper to mark the injection site, and the class of medication (steroid vs. anti-vascular endothelial growth factor). MAIN OUTCOME MEASURES: Cases of presumed infectious endophthalmitis. RESULTS: Thirty-three cases of presumed infectious endophthalmitis occurred after 37 646 injections (0.088%). The method of PI application was found to be a statistically significant predictor of the incidence of endophthalmitis (P = 0.031). When compared with the incidence of endophthalmitis for physicians who did not reapply PI (0.124% [20/16 155]), there was no statistical difference for reapplication of PI without the use of a speculum (0.110% [6/5472]; P = 0.584) or reapplication before speculum insertion (0.122% [5/4067]; P = 0.863). However, reapplication of PI after insertion of the lid speculum was associated with a significantly decreased incidence of endophthalmitis (0.017% [2/11 952]; P = 0.004; odds ratio, 0.113). Use of gloves (P = 0.119) or a caliper to mark the injection site (P = 0.496) and the class of medication (P = 0.740) were not found to be statistically significant risk factors for endophthalmitis development. CONCLUSIONS: The application of PI after placement of the lid speculum reduced the incidence of endophthalmitis occurring after injection approximately 7-fold compared with other aseptic protocols. Preventing the eyelid from contacting the injection site after the final application of PI is an important step in improving the safety of intravitreal injections.

Imaging Characteristics and Natural History of Macular Pseudo-Folds Mimicking Full-Thickness Postoperative Macular Folds Following Retinal Detachment Repair.

BACKGROUND AND OBJECTIVES: Postoperative retinal folds are a rare complication of retinal detachment repair. Folds involving the macula may result in decreased vision, metamorphopsia, and diplopia. There is no consensus on whether symptomatic folds require additional surgery, as both spontaneous regression and permanent vision loss have been described. The authors present three cases of symptomatic macular folds that demonstrated spontaneous resolution and identify key OCT prognostic signs. PATIENTS AND METHODS: The study presented is a retrospective case series. RESULTS: Three patients developed symptomatic postoperative macular folds. Despite funduscopic appearances indistinguishable from full-thickness folds, optical coherence tomography (OCT) imaging revealed that none of the folds involved the full thickness of the retina. All cases demonstrated spontaneous resolution with evidence of visual improvement within 2 months. CONCLUSION: OCT is essential in distinguishing between partial and full-thickness macular folds. The authors propose that partial-thickness folds should be termed "pseudo-folds," which represent a unique entity that has a favorable natural history. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:488-492.].

A Comparison of Sequential Glaucoma Drainage Device Implantation Versus Cyclophotocoagulation Following Failure of a Primary Drainage Device.

PURPOSE: To compare sequential glaucoma drainage device (GDD) implantation with transscleral diode cyclophotocoagulation (CPC) following failure of a primary GDD. MATERIALS AND METHODS: A retrospective review of all patients who underwent GDD implantation at a single institution over 10 years. Patients who required an additional GDD and/or CPC were analyzed. Success was defined as absence of loss of light perception, reoperation for glaucoma, and intraocular pressure (IOP) >21 or <6 at 2 consecutive visits after an initial 3-month period. RESULTS: Thirty-two patients received sequential GDD. Twenty-one underwent CPC. Cohorts were statistically similar in regards to age, sex, race, and number of previous surgeries. Preoperatively, the GDD cohort had a lower IOP and better visual acuity. The mean length of follow-up was 37.9 months for the GDD group and 46.3 months for CPC. Both procedures significantly reduced IOP; however, CPC led to a greater reduction (P=0.0172). Survival analysis found the 5-year probability of surgical success to be 65.3% for sequential GDD and 58.0% for CPC (P=0.8678). No cases of phthisis occurred in either group. There were 2 cases of endophthalmitis (6.3%) in the GDD group, and none in the CPC group. In eyes without preexisting corneal edema, estimated corneal decompensation probability at 3 years was 31.6% for GDD and 6.7% for CPC (P=0.0828). CONCLUSIONS: Sequential GDD and CPC are both effective at reducing IOP following the failure of a primary GDD. CPC after GDD failure warrants further investigation as it led to a greater reduction in IOP with fewer serious adverse events.

Physical Activity and Quality of Life in Retinitis Pigmentosa.

PURPOSE: Aerobic exercise has been found to be neuroprotective in animal models of retinal degeneration. This study aims to report physical activity levels in patients with RP and investigate the relationship between physical activity and vision-related quality-of-life (QOL). MATERIALS AND METHODS: A retrospective study of adult patients with RP examined in 2005-2014. Physical activity levels were assessed using the Godin Exercise Questionnaire. The NEI-Visual Function Questionaire-25 (VFQ-25), SF-36 General Health survey, and Pepper Assessment Tool for Disability (PAT-D) were administered. RESULTS: 143 patients participated. 81 (56.6%) patients were classified as "active" and 62 (43.4%) as "insufficiently active" by Godin score. VFQ-25 revealed statistically significant differences between the active and insufficiently active patients, including overall visual function (53.3 versus 45.1, p = 0.010), color vision (73.8 versus 52.9, p < 0.001), and peripheral vision (34.3 versus 23.8, p = 0.021). The physical component of the SF-36 and the PAT-D survey also demonstrated statistically significant differences (47.2 versus 52.9, p = 0.002; 24.3 versus 30.0, p = 0.010). Active patients had a higher initial Goldmann visual field (GVF) score (74.8 versus 60.1 degrees, p = 0.255) and final GVF score (78.7 versus 47.1 degrees, p = 0.069) but did not reach statistical significance. CONCLUSIONS: In RP, increased physical activity is associated with greater self-reported visual function and QOL.

Diffuse bilateral retinal hemorrhages in an infant with a coagulopathy and prolonged cardiopulmonary resuscitation.

We report a case of diffuse bilateral retinal and optic nerve sheath hemorrhages in an 8-week-old boy who was found unresponsive. The child underwent prolonged cardiopulmonary resuscitation and was noted on admission to have a coagulopathy. An autopsy determined the cause of death to be a myocardial infarct in the distribution of an anomalous coronary artery. This case demonstrates the difficulty that may occur in establishing whether child abuse caused death in the setting of another potential cause of mortality.

MULTIMODAL IMAGING OF A FAMILY WITH SPINOCEREBELLAR ATAXIA TYPE 7 DEMONSTRATING PHENOTYPIC VARIATION AND PROGRESSION OF RETINAL DEGENERATION.

PURPOSE: To report the variability and progression of clinical presentation in three family members with spinocerebellar ataxia Type 7 including early recognizable features on retinal imaging and magnetic resonance imaging. METHODS: Retrospective case series. RESULTS: The proband, Patient 1 (mother) presented at age 26 with light perception vision. Initial examination was significant for optic disc pallor, vascular attenuation, and central macular atrophy. Two years later, her vision declined to no light perception, and fundus examination demonstrated marked progression of macular atrophy and peripheral bone spicule formation. Seven years after the onset of vision loss, neurologic examination demonstrated ataxia, dysarthria, and slowed saccades. Genetic testing of ATXN7 identified heterozygous 61-CAG trinucleotide repeat expansion confirming the diagnosis of spinocerebellar ataxia Type 7. Patient 2 (son) presented at age 11 with visual acuity of 20/300 bilaterally and decreased color vision. Funduscopic examination was notable for disc pallor, vascular attenuation, and peripheral pigmentary changes. Electroretinography demonstrated diminished rod and cone function, and Goldmann visual field testing revealed paracentral scotoma. Patient 3 (daughter) presented at age 14 with visual acuity of 20/50 bilaterally and minimal funduscopic changes. The only significant ophthalmic finding was retinal thinning with atrophy of the outer nuclear layer and subfoveal ellipsoid zone on optical coherence tomography. Early cerebellar volume loss was also noted on magnetic resonance imaging. CONCLUSION: The clinical presentation of spinocerebellar ataxia Type 7 can vary widely even within the same family. In individuals with vision loss and normal fundus examination, careful evaluation of optical coherence tomography and brain magnetic resonance imaging facilitates early diagnosis and genetic testing.

New players tip the scales in the balance between excitatory and inhibitory synapses.

Synaptogenesis is a highly controlled process, involving a vast array of players which include cell adhesion molecules, scaffolding and signaling proteins, neurotransmitter receptors and proteins associated with the synaptic vesicle machinery. These molecules cooperate in an intricate manner on both the pre- and postsynaptic sides to orchestrate the precise assembly of neuronal contacts. This is an amazing feat considering that a single neuron receives tens of thousands of synaptic inputs but virtually no mismatch between pre- and postsynaptic components occur in vivo. One crucial aspect of synapse formation is whether a nascent synapse will develop into an excitatory or inhibitory contact. The tight control of a balance between the types of synapses formed regulates the overall neuronal excitability, and is thus critical for normal brain function and plasticity. However, little is known about how this balance is achieved. This review discusses recent findings which provide clues to how neurons may control excitatory and inhibitory synapse formation, with focus on the involvement of the neuroligin family and PSD-95 in this process.

Glaucoma drainage devices: risk of exposure and infection.

PURPOSE: To identify risk factors for device exposure and intraocular infection following implantation of a glaucoma drainage device. DESIGN: Retrospective case series. METHODS: The medical records of adult patients undergoing glaucoma drainage device implantation at an academic medical center between 2000 and 2010 were reviewed. Main outcome measures included device exposure and intraocular infection. RESULTS: Seven hundred and sixty-three cases were identified. These included 702 primary implants (ie, the first drainage device implanted into an eye) and 61 sequential implants. Among 702 primary implants, there were 41 cases of exposure (5.8%). None of the potential risk factors were statistically significant. Implant location was found to be a marginally significant risk factor. The exposure rates for inferior and superior implants were 12.8% (5 of 39) and 5.4% (36 of 663), respectively (P = .056). The highest rate of exposure for primary implants occurred in the inferior-nasal quadrant (17.2%, 5 of 29). The rate of exposure for sequential devices was 13.1% (8 of 61), with the highest rate also found in the inferior-nasal quadrant (20%, 5 of 25). Of 49 total exposures, 8 were associated with intraocular infection (16.3%). Exposures over inferior implants were more likely to be associated with infection than exposures over superior implants (41.7% vs 8.1%; P = .0151). CONCLUSION: Implant location approached, but did not reach, statistical significance as a risk factor for exposure. Exposures over inferior implants place patients at a higher risk of infection than superior exposures. More studies are needed to identify modifiable risk factors for device exposure.

Modulation of dopamine mediated phosphorylation of AMPA receptors by PSD-95 and AKAP79/150.

Communication between dopaminergic and glutamatergic synapses is critical for several functions related to cognition and emotion. Here, we examined whether dopamine receptor activity regulates phosphorylation and trafficking of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor subunit, GluR1. We find treatment with a dopamine D1 receptor agonist enhanced GluR1 phosphorylation at Ser845, the PKA phosphorylation site, in both striatal and prefrontal cortical neurons. Enhanced phosphorylation of GluR1 also correlated with increased amounts of GluR1 on the cell surface. These effects were disrupted by expression of mutant forms of the A-kinase anchoring protein (AKAP79/150) and the postsynaptic density protein, PSD-95, that fail to target synaptic sites. Similar enhancement of the phosphorylation of GluR1 was observed in the nucleus accumbens upon stimulation of dopamine release in vivo using electrical stimulation of dopamine cell bodies in the ventral tegmental area. These results suggest in vivo stimulation of dopamine release directly influences AMPA receptor phosphorylation and together with in vitro data indicate that coupling of the AMPA receptor to AKAP79/150 and PSD-95 modulate this process.