Defining permeability of curved membranes in molecular dynamics simulations.

Many phospholipid membranes in the cell have a high curvature; for instance, in caveolae, mitochondrial crystae, nanotubes, membrane pearls, small liposomes, or exosomes. Molecular dynamics (MD) simulations are a computational tool to gain insight in the transport behavior at the atomic scale. Membrane permeability is a key kinetic property that might be affected in these highly curved membranes. Unfortunately, the geometry of highly curved membranes creates ambiguity in the permeability value, even with an arbitrarily large factor purely based on geometry, caused by the radial flux not being a constant value in steady state. In this contribution, the ambiguity in permeability for liposomes is countered by providing a new permeability definition. First, the inhomogeneous solubility diffusion model based on the Smoluchowski equation is solved analytically under radial symmetry, from which the entrance and escape permeabilities are defined. Next, the liposome permeability is defined guided by the criterion that a flat and curved membrane should have equal permeability, in case these were to be carved out from an imaginary homogeneous medium. With this criterion, our new definition allows for a fair comparison of flat and curved membranes. The definition is then transferred to the counting method, which is a practical computational approach to derive permeability by counting complete membrane crossings. Finally, the usability of the approach is illustrated with MD simulations of diphosphatidylcholine (DPPC) bilayers, without or with some cholesterol content. Our new liposome permeability definition allows us to compare a spherically shaped membrane with its flat counterpart, thus showcasing how the curvature effect on membrane transport may be assessed.

Capric Acid and Myristic Acid Permeability Enhancers in Curved Liposome Membranes.

Liposomes are considered as advanced drug delivery systems for cancer treatment. A generation of pH-sensitive liposomes is being developed that use fatty acids (FAs) as a trigger for drug release in tumor tissues. However, FAs are also known to enhance permeability, and it is unclear whether FAs in liposomes may cause drug leakage or premature drug release. The passive permeability of the drug through the membrane of the liposome is thus a crucial factor for timely drug delivery. To investigate how the curvature and lipid composition of liposomes affect their passive permeability, coarse-grained molecular dynamics were performed. The permeability was determined with a counting method. Flat bilayers and three liposomes with varying diameters were studied, which had varying lipid compositions of dipalmitoylphosphatidylcholine, cholesterol, and deprotonated or neutral saturated FAs. The investigated permeants were water and two other small permeants, which have different free energy profiles (solubility) across the membrane. First, for the curvature effect, our results showed that curvature increases the water permeability by reducing the membrane thickness. The permeability increase for water is about a factor of 1.7 for the most curved membranes. However, a high curvature decreases permeability for permeants with free energy profiles that are a mix of wells and barriers in the headgroup region of the membrane. Importantly, the type of experimental setup is expected to play a dominant role in the permeability value, i.e., whether permeants are escaping or entering the liposomes. Second, for the composition effect, FAs decrease both the area per lipid (APL) and the membrane thickness, resulting in permeability increases of up to 55%. Cholesterol has a similar effect on the APL but has the opposite impact on membrane thickness and permeability. Therefore, FAs and cholesterol have opposing effects on permeability, with cholesterol's effect being slightly stronger in our simulated bilayers. As all permeability values were well within a factor of 2, and with liposomes usually being larger and less curved in experimental applications, it can be concluded that the passive drug release from a pH-sensitive liposome does not seem to be significantly affected by the presence of FAs.

Understanding the Role of Caveolae in Oxygen Buffering: The Effect of Membrane Curvature.

The "oxygen paradox" can be explained as two opposing biological processes with oxygen (O2) as a reactant. On the one hand, oxygen is essential to aerobic metabolism, powering oxidative phosphorylation in mitochondria. On the other hand, an excess supply of oxygen will generate reactive species which are harmful for the cell. In healthy tissues, the first process must be maximized relative to the second one. We have hypothesized that curved and cholesterol-enriched membrane invaginations called caveolae help maintain the proper oxygen level by taking up oxygen and attenuating its release to the mitochondria. The mechanism by which caveolae may help to buffer the oxygen level in cells is still unclear. Here, we aim to assess how structural aspects of caveolae, the curvature of the membrane, influence the local oxygen abundance and the membrane partitioning. We have modelled a flat bilayer and a liposome composed of dipalmitoylphosphatidylcholine (DPPC), using molecular dynamics simulation. Associated changes in the membrane-level oxygen partition coefficient and free energy profiles will be presented.

Preventive factors, diagnosis, and management of injection-related endophthalmitis: a literature review.

BACKGROUND: Intravitreal medication injections represent the gold standard treatment for a variety of potentially blinding chorioretinal vascular diseases. Despite their excellent safety profile, they are associated with the feared complication of injection-related endophthalmitis (IRE). Though the overall incidence of IRE is low, due to the ever-increasing number of injections being performed, it is a complication that all retina specialists are likely to encounter. This article reviews various factors that could potentially influence the risk of IRE and discusses evidence-based strategies for management. METHOD: PubMed was searched for keywords "intravitreal injection" and "endophthalmitis" from the period of 1995-2021. Relevant articles were reviewed and selected articles were analyzed with respect to the incidence, potential preventive factors, clinical presentation, microbial profile, management, and outcomes for IRE. RESULTS: There is strong consensus supporting the use of povidone iodine topical antiseptic, eyelid retraction away from the injection site, and avoiding treatment of eyes with active surface or eyelid disease, but there is less agreement on the use of face masks versus "no-talking" policies and optimal anesthetic technique. Current evidence comparing tap and inject or early vitrectomy for treatment of IRE is inadequate to determine an optimal treatment strategy. CONCLUSION: Intravitreal injections are sight saving, but even using established prophylactic measures there remains a small but real risk of infectious injection-related complications. Further investigations comparing tap and inject versus vitrectomy may help to establish optimal treatment, although the rarity of IRE makes designing adequately powered prospective trials a difficult task.

Sampling efficiency of the counting method for permeability calculations estimated with the inhomogeneous solubility-diffusion model.

Permeability is a key property in various fields such as membrane technology for chemical separation and transport of substances through cell membranes. At the molecular scale, the counting method uses the number of membrane crossings in a conventional unbiased molecular dynamics simulation to predict the permeability. This contribution investigates under which conditions the counting method has insufficient statistics. An equation is derived for a compartmental model based on the inhomogeneous solubility-diffusion (Smoluchowski) model, giving insight into how the flux correlates with the solubility of permeants. This equation shows that a membrane crossing is a rare event not only when the membrane forms a large free energy barrier but also when the membrane forms a deep free energy well that traps permeants. Such a permeant trap has a high permeability; yet, the counting method suffers from poor statistics. To illustrate this, coarse-grained MD was run for 16 systems of dipalmitoylphosphatidylcholine bilayer membranes with different permeant types. The composition rule for permeability is shown to also hold for fluxes, and it is highlighted that the considered thickness of the membrane causes uncertainty in the permeability calculation of highly permeable membranes. In conclusion, a high permeability in itself is not an effective indicator of the sampling efficiency of the counting method, and caution should be taken for permeants whose solubility varies greatly over the simulation box. A practical consequence relevant in, e.g., drug design is that a drug with high membrane permeability might get trapped by membranes thus reducing its efficacy.

Optical coherence tomography angiography changes in macula-off rhegmatogenous retinal detachments repaired with silicone oil.

PURPOSE: To evaluate the changes on optical coherence tomography angiography (OCTA) in macula-off rhegmatogenous retinal detachments (RRD) treated with pars plana vitrectomy (PPV) and silicone oil (SO) 5000-cSt tamponade. MATERIALS AND METHOD: Forty-five eyes with macula-off RRD treated with PPV and SO tamponade were enrolled with the fellow eye being used as a control. OCT-A was obtained using the RTVue XR 100 Avanti (Optovue, Inc., Fremont, CA, USA) at the 1-week, 1-month, and 3-month postoperative visit. Retinal vascular density, choroidal flow area, retinal thickness, and foveal avascular zone area were evaluated at each follow-up visit. Changes in these parameters in the postoperative eye were tracked at each follow-up visit as were the relative differences between the postoperative eye and the contralateral eye. RESULTS: Vascular density of parafoveal superficial capillary plexus and total retina demonstrated significant decrease in the postoperative silicone-filled eye when compared to the fellow eye (P < 0.0001). Although there was some improvement in these values at subsequent follow-ups, they remained less than the fellow eye. Foveal (P = 0.002) and parafoveal (P < 0.0001) thickness were less than the fellow eye. Choroidal flow area did not show a significant change in operated eye compared with the fellow eye. CONCLUSION: Eyes with macula-off RRD repaired with PPV and SO, at 3-month follow-up, demonstrated less retinal vascular density at parafoveal area as well as lower retinal thickness at fovea when compared to the healthy fellow eyes.

Evaluation of Effects of Health Literacy, Numeracy Skills, and English Proficiency on Health Outcomes in the Population of People With Diabetes in East Harlem.

IN BRIEF In the management of diabetes, adequate health literacy is necessary to help patients monitor their caloric and carbohydrate intake and monitor their blood glucose to achieve adequate glycemic control. This cross-sectional study was conducted to assess the health literacy of patients with diabetes from East Harlem in New York City using the validated Newest Vital Sign screening tool and to investigate its association with microvascular complications of diabetes. Lower health literacy was found to be associated with higher microvascular complications in these patients with diabetes.

Association of genetic variants in RAB23 and ANXA11 with uveitis in sarcoidosis.

Purpose: Uveitis occurs in a subset of patients with sarcoidosis. The purpose of this study was to determine whether genetic variants that have been associated previously with overall sarcoidosis are associated with increased risk of developing uveitis. Methods: Seventy-seven subjects were enrolled, including 45 patients diagnosed with sarcoidosis-related uveitis as cases and 32 patients with systemic sarcoidosis without ocular involvement as controls. Thirty-eight single nucleotide polymorphisms (SNPs) previously associated with sarcoidosis, sarcoidosis severity, or other organ-specific sarcoidosis involvement were identified. Allele frequencies in ocular sarcoidosis cases versus controls were compared using the chi-square test, and p values were corrected for multiple hypotheses testing using permutation. All analyses were conducted with PLINK. Results: SNPs rs1040461 and rs61860052, in ras-related protein RAS23 (RAB23) and annexin A11 (ANXA11) genes, respectively, were associated with sarcoidosis-associated uveitis. The T allele of rs1040461 and the A allele of rs61860052 were found to be more prevalent in ocular sarcoidosis cases. These associations remained after correction for the multiple hypotheses tested (p=0.01 and p=0.02). In a subanalysis of Caucasian Americans only, two additional variants within the major histocompatibility complex (MHC) genes on chromosome 6, in HLA-DRB5 and HLA-DRB1, were associated with uveitis as well (p=0.009 and p=0.04). Conclusions: Genetic variants in RAB23 and ANXA11 genes were associated with an increased risk of sarcoidosis-associated uveitis. These loci have previously been associated with overall sarcoidosis risk.

Structural Changes Associated with Delayed Dark Adaptation in Age-Related Macular Degeneration.

PURPOSE: To examine the relationship between dark adaptation (DA) and optical coherence tomography (OCT)-based macular morphology in age-related macular degeneration (AMD). DESIGN: Prospective, cross-sectional study. PARTICIPANTS: Patients with AMD and a comparison group (>50 years) without any vitreoretinal disease. METHODS: All participants were imaged with spectral-domain OCT and color fundus photographs, and then staged for AMD (Age-related Eye Disease Study system). Both eyes were tested with the AdaptDx (MacuLogix, Middletown, PA) DA extended protocol (20 minutes). A software program was developed to map the DA testing spot (2° circle, 5° superior to the fovea) to the OCT B-scans. Two independent graders evaluated the B-scans within this testing spot, as well as the entire macula, recording the presence of several AMD-associated abnormalities. Multilevel mixed-effects models (accounting for correlated outcomes between 2 eyes) were used for analyses. MAIN OUTCOME MEASURES: The primary outcome was rod-intercept time (RIT), defined in minutes, as a continuous variable. For subjects unable to reach RIT within the 20 minutes of testing, the value of 20 was assigned. RESULTS: We included 137 eyes (n = 77 subjects), 72.3% (n = 99 eyes) with AMD and the remainder belonging to the comparison group. Multivariable analysis revealed that even after adjusting for age and AMD stage, the presence of any abnormalities within the DA testing spot (ß = 4.8, P < 0.001), as well as any abnormalities in the macula (ß = 2.4, P = 0.047), were significantly associated with delayed RITs and therefore impaired DA. In eyes with no structural changes within the DA testing spot (n = 76, 55.5%), the presence of any abnormalities in the remaining macula was still associated with delayed RITs (ß = 2.00, P = 0.046). Presence of subretinal drusenoid deposits and ellipsoid zone disruption were a consistent predictor of RIT, whether located within the DA testing spot (P = 0.001 for both) or anywhere in the macula (P < 0.001 for both). Within the testing spot, the presence of classic drusen or serous pigment epithelium detachment was also significantly associated with impairments in DA (P ≤ 0.018). CONCLUSIONS: Our results suggest a significant association between macular morphology evaluated by OCT and time to dark-adapt. Subretinal drusenoid deposits and ellipsoid zone changes seem to be strongly associated with impaired dark adaptation.

Retinal pigmentary changes in chronic uveitis mimicking retinitis pigmentosa.

PURPOSE: To present retinal pigmentary changes mimicking retinitis pigmentosa (RP) as a finding of advanced uveitis. METHODS: We retrospectively reviewed charts of patients without a family history of inherited retinal degenerations who presented with retinal pigment changes and signs of past or present intraocular inflammation. Comprehensive eye examination including best-corrected visual acuity, slit-lamp examination and dilated fundus examination was performed on all patients in addition to color fundus photography, optical coherence tomography, fluorescein angiography (FA), and full-field electroretinogram testing. RESULTS: We identified five patients with ages ranging from 33 to 66 years, who presented with RP-like retinal pigmentary changes which were eventually attributed to longstanding uveitis. The changes were bilateral in three cases and unilateral in two cases. Four of five cases presented with active inflammation, and the remaining case showed evidence of active intraocular inflammation during follow-up. CONCLUSION: This study highlights the overlapping features of advanced uveitis and RP including the extensive pigmentary changes. Careful review of possible past uveitis history, detailed examination of signs of past or present inflammation and ancillary testing, with FA often being most helpful, are required for the correct diagnosis. This is important, because intervention can prevent further damage if the cause of the pigmentary changes is destructive inflammation.

Pre-papillary vitreous opacities associated with Behçet's disease: a case series and review of the literature.

PURPOSE: To present pre-papillary vitreous opacity as an uncommon manifestation of inflammation in Behçet's disease that may be specific to this uveitic entity. METHODS: We retrospectively reviewed the charts of 67 patients with Behçet's disease examined at our clinic between 2005 and 2016. Behçet's disease was diagnosed based on established clinical criteria of inflammation involving the eyes, mucocutaneous junctions, and skin. Patients with Behçet's disease who presented with papillitis and a pre-papillary vitreous opacity were identified. Response to anti-inflammatory treatment on examination and optical coherence tomography imaging were evaluated. PubMed searches were performed for (1) other cases with pre-papillary vitreous opacities in uveitic entities and (2) reports of optic nerve involvement specifically in Behçet's disease. RESULTS: We identified three patients with Behçet's disease who presented with unilateral papillitis and a pre-papillary vitreous opacity. The pre-papillary vitreous opacity had a funnel-shaped appearance on optical coherence tomography. All patients were initially treated with steroids, which led to resolution of the opacity clinically and on imaging. We identified one previous report of such a pre-papillary opacity in a patient with Behçet's disease, and no reports of this finding in other uveitic entities. CONCLUSION: This study expands the number of Behçet's disease cases presenting with a pre-papillary vitreous opacity and demonstrates novel optical coherence imaging of this finding. This finding may be specific to Behçet's disease as it was not identified in other uveitic entities in a review of the existing literature.

Association of serum lipid levels with retinal hard exudate area in African Americans with type 2 diabetes.

PURPOSE: Previous studies have yielded conflicting results regarding whether serum lipid levels are associated with retinal hard exudates in diabetic retinopathy. The majority of studies have assessed hard exudates only as a dichotomous trait (presence vs. absence) and included limited numbers of African Americans (AA). The purpose of this study was to determine if there are any associations between serum lipid levels and hard exudates in AA with type 2 diabetes (T2D). METHODS: 890 AA participants with T2D were enrolled from 5 sites. Macular fundus photographs were graded by masked ophthalmologist investigators. Hard exudate areas were measured using a semi-automated algorithm and ImageJ software. Multivariate regression models were used to determine the association between serum lipid levels and (1) presence of hard exudate and (2) area of hard exudate. RESULTS: Presence of hard exudates was associated with higher total cholesterol [(odds ratio (OR) = 1.08, 95 % confidence interval (CI) 1.03-1.13, P = 0.001)] and higher low-density lipoprotein (LDL) cholesterol (OR = 1.08, 95 % CI 1.03-1.14, P = 0.005) in models controlling for other risk factors. Hard exudate area was also associated with both higher total and LDL cholesterol levels (P = 0.04 and 0.01, respectively) in multivariate models controlling for other risk factors. CONCLUSIONS: Higher total and LDL cholesterol were associated with the presence of hard exudates and a greater hard exudate area in AA with T2D. This information can be used to counsel diabetic patients regarding the importance of lipid control to decrease the risk of macular hard exudates.

OPTICAL COHERENCE TOMOGRAPHY CHARACTERISTICS OF MACULAR EDEMA AND HARD EXUDATES AND THEIR ASSOCIATION WITH LIPID SERUM LEVELS IN TYPE 2 DIABETES.

PURPOSE: To determine whether hyperreflective foci (HF) and macular thickness on spectral domain ocular coherence tomography are associated with lipid levels in patients with Type 2 diabetes. METHODS: Two hundred and thirty-eight participants from four sites had fundus photographs and spectral domain ocular coherence tomography images graded for hard exudates and HF, respectively. Regression models were used to determine the association between serum lipid levels and 1) presence of HF and hard exudates and 2) central subfield macular thickness, central subfield macular volume, and total macular volume. RESULTS: All patients with hard exudates on fundus photographs had corresponding HF on spectral domain ocular coherence tomography, but 57% of patients with HF on optical coherence tomography did not have hard exudates detected in their fundus photographs. Presence of HF was associated with higher total cholesterol (odds ratio = 1.13, 95% confidence interval = 1.01-1.27, P = 0.03) and higher low-density lipoprotein levels (odds ratio = 1.17, 95% confidence interval = 1.02-1.35, P = 0.02) in models adjusting for other risk factors. The total macular volume was also associated with higher total cholesterol (P = 0.009) and triglyceride (P = 0.02) levels after adjusting for other risk factors. CONCLUSION: Higher total and low-density lipoprotein cholesterol were associated with presence of HF on spectral domain ocular coherence tomography. Total macular volume was associated with higher total cholesterol and triglyceride levels.

Effect of race and ethnicity on surgical outcomes for rhegmatogenous retinal detachments.

OBJECTIVE: To evaluate the effect of socioeconomic and demographic factors on outcomes in rhegmatogenous retinal detachments (RRDs). DESIGN: Retrospective cohort study. METHODS: A total of 71 white and 124 black and/or Hispanic patients who had surgical repair of RRDs between October 2013 and September 2021 at a single-centre safety net hospital. Main outcomes were single surgery success rates (SSSR) and postoperative visual acuity at 6-month and final follow-up. RESULTS: Black and (or) Hispanic patients were significantly younger (black and [or] Hispanic, 50.7 years vs white, 57.6 years; p = 0.003), had lower mean household incomes (black and [or] Hispanic, $80,932 vs white, $92,911; p = 0.007), were more likely to have more than 1 retinal break (black and [or] Hispanic, 65% vs white, 49%; p = 0.04), and had higher rates of proliferative vitreoretinopathy (PVR) at presentation (black and [or] Hispanic, 35% vs white, 18%; p = 0.02). SSSR was similar (black and [or] Hispanic, 73.4% vs white, 73.2%; p = 0.98), but black and (or) Hispanic patients had worse visual acuity postoperatively (black and [or] Hispanic, 20/63 vs white, 20/40 at final follow-up; p = 0.03). While race was linked to visual outcome in univariate testing; multivariate analysis revealed only macula status (p = 0.007 at 6 months; p = 0.01 at final follow-up), presence of PVR (p < 0.001 at both time points), and SSSR (p = 0.003 at final follow-up) as predictors of worse visual outcomes. CONCLUSIONS: Preoperative factors such as higher rates of PVR may contribute to worse vision outcomes in black and (or) Hispanic patients undergoing surgical repair for RRD.

Penicillin Responsive Presumed Seronegative Ocular Syphilis in a Patient with Human Immunodeficiency Virus: A Case Report and Review of the Literature.

Ocular and systemic syphilis are well known to mimic other clinical entities making them challenging to diagnose in many cases. Syphilis testing plays an important role in diagnosis and timely treatment. Here we describe a patient with untreated human immunodeficiency virus (HIV) infection who presented with bilateral panuveitis with repeatedly negative syphilis serologies. In light of worsening retinitis while on aggressive anti-viral treatment and in consideration of the clinical suspicion for syphilitic uveitis, intravenous penicillin was initiated empirically. The patient demonstrated significant improvement subjectively and objectively after treatment. We also review and discuss syphilis testing reliability generally and in HIV co-infected patients in particular. Empiric intravenous penicillin should be considered in patients with clinical features of ocular syphilis despite negative serologic testing, especially in those with HIV co-infection.

Demographic and socioeconomic disparities in the hybrid ophthalmology telemedicine model.

IMPORTANCE: As telemedicine use expands, it is important to evaluate demographic and socioeconomic disparities among patients receiving ophthalmic care through new hybrid telemedicine models. OBJECTIVE: To evaluate whether there are demographic and socioeconomic disparities in the delivery of the hybrid telemedicine model. DESIGN: Retrospective, cross-sectional, case-control analysis of patient encounters from April to December 2020. SETTING: A single, academic, hospital-based eye clinic in Boston, Massachusetts. METHODS: Electronic medical records of all patient encounters from April to December 2020 were reviewed and categorized into hybrid, virtual-only, and standard in-person visits. Patient-level data for all visits were extracted including age, sex, race/ethnicity, primary language, Area Deprivation Index (ADI), insurance type, and marital status. Visit-level data for all hybrid visits were also extracted from the medical record including the visit dates and patient adherence. Demographics for the cohort of patients with at least one no-show visit were compared with demographics for the cohort of patients who only had completed visits. The primary study outcomes were the differences in demographic characteristics between the hybrid visit show and no-show groups. The secondary outcomes included demographic characteristics of patients who did not complete their hybrid visit versus a time-matched cohort of patients who did not complete their standard in-person visit. Continuous variables for patient characteristics were compared with independent samples t-tests and categorical variables were compared using Pearson chi-square tests. Multivariate logistic regression was used to examine the differences between the cohorts. Variables with missing values other than suppressed ADI values were imputed using multiple imputations by chained equations. RESULTS: Of a total of 1025 patients who were scheduled for a hybrid visit, 145 (14.1%) patients failed to complete their visit. Primary language and insurance were found to be statistically different between patients who completed and did not complete their hybrid visits. More English speakers and fewer Haitian Creole speakers completed their hybrid visits (p = 0.007) while more patients with private insurance and fewer patients with Medicaid completed their hybrid telemedicine visits (p = 0.026). No associations were found between hybrid telemedicine visit adherence and age, sex, race/ethnicity, marital status, or ADI. When the 145 patients who failed to complete their hybrid visits were compared to a time-matched cohort of patients who failed to complete their standard in-person visit, we found that patients who missed hybrid visits were similar to those who missed standard in-person visits except for patients insured by Medicare. These patients were more likely to miss a hybrid visit than a standard in-person visit (Odds Ratio 2.199, 95% confidence interval 1.136-4.259, p = 0.019). No associations were found between patient nonadherence with hybrid telemedicine versus with standard in-person visits based on age, sex, primary language, race/ethnicity, marital status, or ADI. CONCLUSION: The hybrid telemedicine model was associated with insurance and language-based disparities. Patients with non-English primary language and Medicaid recipients were more likely to miss a hybrid visit than their counterparts. Our findings support developing deliberate interventions to ensure hybrid telemedicine care is delivered equitably to all patients.

Socioeconomic Disparities in Patients Receiving Intravitreal Injections for Age-Related Macular Degeneration Amid the COVID-19 Pandemic.

Purpose: To determine the effects of socioeconomic factors on visit adherence and the resultant visual outcomes for patients receiving intravitreal injections for neovascular age-related macular degeneration during the COVID-19 pandemic. Methods: In this retrospective case-control study, medical records were reviewed to collect appointment attendance, age, sex, self-reported race/ethnicity, primary language, marital status, insurance, distance from clinic, and Area Deprivation Index (ADI), a measure of socioeconomic disadvantage. Multivariate regression models were created to determine differences in socioeconomic factors between individuals who attended (show group) and those who did not attend (no-show group) appointments. Results: The study enrolled 126 patients in the show group and 115 in the no-show group. On univariate analysis, nonadherence was significantly higher in non-White patients than in White patients (P = .04), urban sites than in suburban sites (P = 1.7 × 10-4), and non-English-speaking patients than in English-speaking patients (P = 4.0 × 10-3). The associations remained significant in multivariate analysis for non-English-speaking patients (P = .03) and urban-site patients (P = .01) after adjusting for age, sex, self-reported race/ethnicity, primary language, marital status, insurance, distance from clinic, site of visit, and ADI. At 6 months and 1 year, a 1-, 2-, and 3-line vision loss was significantly higher in the no-show group than in the show group on univariate and multivariate analysis after adjusting for age, sex, race, lens status, and presence of glaucoma and diabetic retinopathy. Conclusions: Non-English-speaking patients and urban-based patients were less likely to present for intravitreal injection appointments during the initial peak of the COVID-19 pandemic. This disparity translated to worse vision outcomes at 6 months and 1 year.

Choroidal Metastasis With Secondary Retinal Detachment in a Man With BCRA2-Associated Breast Adenocarcinoma.

Breast cancer with ocular metastasis is rare in men. Such cases with BRCA2 gene mutation are even less common. This case report describes a 59-year-old man with recently diagnosed breast adenocarcinoma who presented for surgical repair of a retinal detachment in his left eye. Clinical exanimation revealed a left inferior retinal detachment without a clear retinal break. Spectral-domain optical coherence tomography (SD-OCT) of the left macula showed sub-retinal fluid extending into the fovea and a thickened choroid. B-scan ultrasonography was obtained and showed a diffuse inferior choroid mass measuring 5 millimeters (mm) at the apex with an overlying retinal detachment, consistent with breast cancer metastasis to the choroid. He was initiated on chemotherapy and whole-brain radiation with symptomatic improvement. This case illustrates the importance of obtaining a thorough medical history and additional testing when indicated.

Non-cystic macular thickening on optical coherence tomography as an alternative to fluorescein angiography for predicting retinal vascular leakage in early stages of uveitis.

To evaluate the relationship between non-cystic thickening of the macula on optical coherence tomography (OCT) and retinal vascular leakage on fluorescein angiogram (FA) in patients with uveitis. A cross-sectional study of patients seen in the uveitis clinic. Patients with any degree of inflammatory cells in the anterior vitreous were included, provided that no macular cyst or subretinal fluid or macular atrophy was observed in OCT. The correlation between OCT features and best corrected visual acuity (BCVA), the degree of inflammation, and FA findings were examined. The severity of vascular leakage in FA was graded for optic nerve, macula and posterior and peripheral leakage. We used generalized estimation equation to assess the associations between macular thickness and volume with angiographic scores. A total of 43 patients (100 exam data) met inclusion criteria. There was a significant relationship between OCT parameters (central macular thickness, 3 mm and 6 mm perifoveal macular thickness as well as total and central macular volume) with angiographic scores (macular, optic disc, posterior and peripheral vascular leakage score) (all P values < 0.0001). The correlation between the 6 mm perifoveal thickness and peripheral vascular leakage score (R = 0.76; P < 0.001) was stronger than the correlation of CMT with this angiographic score (R = 0.69; P < 0.001). Non-cystic thickening of the macula on OCT, especially in perifoveal area, is a reliable predictor of the presence of retinal vascular leakage in patients with uveitis.

Validation of the Postnatal Growth and Retinopathy of Prematurity (GROP) screening criteria.

Background: Retinopathy of prematurity (ROP) is a leading cause of irreversible blindness in infants. The Postnatal Growth and ROP (G-ROP) study proposed new screening criteria for ROP. This study aimed to validate the G-ROP screening criteria in a group of Iranian premature infants who were treated in the neonatal intensive care unit (NICU) for at least 40 days. Methods: In this retrospective study, we extracted the data pertaining to infants admitted to the NICU from January 2020 to December 2021. We screened all the included infants for ROP based on the Iranian national screening criteria. We applied the G-ROP criteria to our study population, and if no criterion was met, the infant was exempted from ROP screening. We determined the sensitivity and specificity of the G-ROP guidelines for ROP detection, along with its capacity for predicting the requirement for ROP treatment. Moreover, we compared the G-ROP guidelines with the Iranian and North American guidelines for ROP screening. Results: A total of 166 premature infants with complete datasets were included: 130 had ROP, of whom 61 were treated. There were 109 female infants (65.7%). The mean (standard deviation [SD]) birth weight and gestational age were 1080 (256) g and 28.28 (1.97) weeks, respectively. Applying the G-ROP criteria, 127 of 130 infants with ROP were identified (sensitivity, 97.69%; 95% confidence interval [CI], 95.11% - 100%), and of 36 infants without ROP, three were correctly excluded (specificity, 8.33%; 95% CI, 0% - 17.36%). The G-ROP criteria did not fail to identify infants who required treatment for ROP (sensitivity, 100%; 95% CI, 98.29 - 100) and had a specificity of 8.69% (95% CI, 2.04% - 15.34%). Although the Iranian and North American criteria had 100% sensitivity for infants with any stage of ROP, they could not detect infants without ROP (0% specificity). Conclusions: The G-ROP screening criteria had a sensitivity of 100% in identifying infants requiring treatment for ROP in our high-risk group; however, specificity was not sufficiently high. Further studies with larger numbers of referred infants could confirm a decrease in the burden of retinal examinations using these criteria.