Leftover Astigmatism: The Missing Link Between Measured and Calculated Posterior Corneal Astigmatism.

PURPOSE: To quantify the total eye astigmatism that is not accounted for by measurement of anterior corneal astigmatism and posterior corneal astigmatism and knowledge of intraocular lens (IOL) astigmatism and assess whether it is correlated with candidate sources of or correlates with leftover astigmatism. METHODS: Vector subtraction of anterior corneal, posterior corneal, and IOL astigmatism from total eye astigmatism as represented by spectacle astigmatism to yield a value of "leftover" astigmatism that is neither corneal nor lenticular. This value was derived in a series of eyes following cataract surgery. This novel entity was examined for correlation with candidate sources of or correlates with leftover astigmatism. RESULTS: In 103 pseudophakic eyes with known IOL toricity, mean leftover astigmatism was 0.71 ± 0.43 diopters. This was significantly correlated with against-the-rule anterior corneal astigmatism (P < .001). CONCLUSIONS: Leftover astigmatism is clinically substantial. Because it is included in IOL cylinder power calculations based on refractive outcome, it may explain why methods of IOL cylinder power calculation using refractive outcome-based adjustments to anterior corneal astigmatism (previously described as adjustments for "posterior corneal astigmatism") are more successful than adjustment on the basis of measured posterior corneal astigmatism. [J Refract Surg. 2022;38(9):559-564.].

Oxidative stress induces ferroptotic cell death in retinal pigment epithelial cells.

The dysfunction and cell death of retinal pigment epithelial (RPE) cells are hallmarks of late-stage dry (atrophic) age-related macular degeneration (AMD), for which no effective therapy has yet been developed. Previous studies have indicated that iron accumulation is a source of excess free radical production in RPE, and age-dependent iron accumulation in RPE is accelerated in patients with dry AMD. Although the pathogenic role of oxidative stress in RPE in the development of dry AMD is widely accepted, the mechanisms of oxidative stress-induced RPE cell death remain elusive. Here, we show that ferroptotic cell death, a mode of regulated necrosis mediated by iron and lipid peroxidation, is implicated in oxidative stress-induced RPE cell death in vitro. In ARPE-19 cells we observed that the ferroptosis inhibitors ferrostatin-1 and deferoxamine (DFO) rescued tert-butyl hydroperoxide (tBH)-induced RPE cell death more effectively than inhibitors of apoptosis or necroptosis. tBH-induced RPE cell death was accompanied by the three characteristics of ferroptotic cell death: lipid peroxidation, glutathione depletion, and ferrous iron accumulation, which were all significantly attenuated by ferrostatin-1 and DFO. Exogenous iron overload enhanced tBH-induced RPE cell death, but this effect was also attenuated by ferrostatin-1 and DFO. Furthermore, mRNA levels of numerous genes known to regulate iron metabolism were observed to be influenced by oxidative stress. Taken together, our observations suggest that multiple modes of cell death are involved in oxidative stress-induced RPE cell death, with ferroptosis playing a particularly important role.

The extent of stretched lamellar cleavage and visual acuity in macular pseudoholes.

BACKGROUND/AIMS: To evaluate the extent of lamellar cleavage and its association with preoperative and postoperative visual acuity (VA) in macular pseudoholes. METHODS: One eye each of 50 patients with macular pseudohole who underwent vitrectomy was retrospectively investigated. Preoperative macular pseudoholes were evaluated using spectral-domain optical coherence tomography (SD-OCT) images taken radially around the central fovea at 30° intervals. The macular pseudoholes were categorised into stage 1 (no cleavage), stage 2 (localised cleavage with (2b) and without (2a) crossing central fovea) and stage 3 (diffuse cleavage). RESULTS: Among the 50 macular pseudoholes, 14, 13, 9 and 14 were categorised into stages 1, 2a, 2b and 3, respectively. The extent of stretched cleavages was associated with worse baseline VA (p=0.0049 by multiple regression model). After surgery, the stretched lamellar cleavage disappeared in 32 patients out of 36 who were postoperatively examined by SD-OCT. In addition, the extensive cleavage (stage 2b/3) independently predicted larger postoperative VA recovery at 3 months by 0.105 logMAR compared with no/mild cleavage (stage 1/2a, p=0.030 by multiple regression model). CONCLUSIONS: Although advanced cleavage in macular pseudohole is associated with worse VA before surgery, even an advanced pseudohole could show favourable visual recovery after surgery.

SUPPLEMENTAL SCLERAL BUCKLE IN VITRECTOMY FOR THE REPAIR OF RHEGMATOGENOUS RETINAL DETACHMENT: A Systematic Review of Literature and Meta-Analysis.

PURPOSE: To evaluate the effect of supplemental scleral buckle (SB) in pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment. METHODS: MEDLINE, EMBASE, and CENTRAL were searched to identify studies comparing PPV with supplemental SB (PPV + SB) to PPV alone for the repair of rhegmatogenous retinal detachment. The outcome measures were primary and final reattachment rates, and postoperative complications. Odds ratio with 95% confidence interval in random effects for the comparison of outcomes between PPV + SB and PPV alone was calculated. RESULTS: Ten studies consisting of 1,704 patients were included. Meta-analysis showed that the overall primary reattachment rate was significantly higher in PPV + SB than PPV alone (odds ratio, 1.70; 95% confidence interval, 1.21-2.39; P = 0.002). The final reattachment rate was equally high in both groups. Postoperative development of epiretinal membrane was more frequent in PPV + SB than in PPV alone (odds ratio, 1.89; 95% confidence interval, 1.30-2.76; P = 0.001), whereas no significant difference in postoperative development of macular edema, proliferative vitreoretinopathy, or elevation of intraocular pressure was found. CONCLUSION: Supplemental SB increases the primary reattachment rate in PPV for rhegmatogenous retinal detachment, although final reattachment rate was equally high with or without SB.

αvß5 Integrin/FAK/PGC-1α Pathway Confers Protective Effects on Retinal Pigment Epithelium.

PURPOSE: To elucidate the mechanism of the induction of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) by photoreceptor outer segments (POS) and its effects on retinal pigment epithelium (RPE). METHODS: PGC-1α upregulation by POS was confirmed in ARPE-19 cells and in RPE ex vivo. To elucidate the mechanism, siRNAs against ß5 integrin, CD36, Mer tyrosine kinase (MerTK), and Atg5, blocking antibodies against CD36 and MerTK, and a specific inhibitor for focal adhesion kinase (FAK) were used. We examined the effect of POS-induced PGC-1α upregulation on the levels of reactive oxygen species (ROS), mitochondrial biogenesis, senescence-associated ß-galactosidase (SA-ß-gal) after H2O2 treatment, and lysosomal activity. Lysosomal activity was evaluated through transcriptional factor EB and its target genes, and the activity of cathepsin D. Lipid metabolism after POS treatment was assessed using Oil Red O and BODIPY C11. RPE phenotypes of PGC-1α-deficient mice were examined. RESULTS: POS-induced PGC-1α upregulation was suppressed by siRNA against ß5 integrin and a FAK inhibitor. siRNAs and blocking antibodies against CD36 and MerTK enhanced the effect of POS on PGC-1α. The upregulation of PGC-1α increased the levels of mRNA for antioxidant enzymes and stimulated mitochondrial biogenesis, decreased ROS levels, and reduced SA-ß-gal staining in H2O2-treated ARPE-19 cells. PGC-1α was critical for lysosomal activity and lipid metabolism after POS treatment. PGC-1α-deficient mice demonstrated an accumulation of type 2 lysosomes in RPE, thickening of Bruch's membrane, and poor choriocapillaris vasculature. CONCLUSIONS: The binding, but not the internalization of POS confers protective effects on RPE cells through the αvß5 integrin/FAK/PGC-1α pathway.

EFFECT OF INTERNAL LIMITING MEMBRANE PEELING DURING VITRECTOMY FOR DIABETIC MACULAR EDEMA: Systematic Review and Meta-analysis.

PURPOSE: To evaluate the effect of internal limiting membrane (ILM) peeling during vitrectomy for diabetic macular edema. METHODS: MEDLINE, EMBASE, and CENTRAL were systematically reviewed. Eligible studies included randomized or nonrandomized studies that compared surgical outcomes of vitrectomy with or without ILM peeling for diabetic macular edema. The primary and secondary outcome measures were postoperative best-corrected visual acuity and central macular thickness. Meta-analysis on mean differences between vitrectomy with and without ILM peeling was performed using inverse variance method in random effects. RESULTS: Five studies (7 articles) with 741 patients were eligible for analysis. Superiority (95% confidence interval) in postoperative best-corrected visual acuity in ILM peeling group compared with nonpeeling group was 0.04 (-0.05 to 0.13) logMAR (equivalent to 2.0 ETDRS letters, P = 0.37), and superiority in best-corrected visual acuity change in ILM peeling group was 0.04 (-0.02 to 0.09) logMAR (equivalent to 2.0 ETDRS letters, P = 0.16). There was no significant difference in postoperative central macular thickness and central macular thickness reduction between the two groups. CONCLUSION: The visual acuity outcomes using pars plana vitrectomy with ILM peeling versus no ILM peeling were not significantly different. A larger randomized prospective study would be necessary to adequately address the effectiveness of ILM peeling on visual acuity outcomes.

Role of Glutathione Peroxidase 4 in Glutamate-Induced Oxytosis in the Retina.

PURPOSE: The purpose of the present study was to investigate the role of glutathione peroxidase 4 (GPx4) in glutamate-induced oxytosis in the retina. METHODS: For in vitro studies, an immortalized rat retinal precursor cell line R28 was used. Cells were transfected with siRNA specifically silencing GPx4 or with scrambled control siRNA. Lipid peroxidation was evaluated by 4-hydroxy-2-nonenal (4-HNE) immunostaining. Cytotoxicity and cell death were evaluated using an LDH activity assay and annexin V staining, respectively. Cells transfected with GPx4 siRNA or control siRNA were treated with glutamate (1 or 2 mM), and the cytotoxicity was evaluated using the LDH activity assay. For in vivo studies, retinal ganglion cell damage was induced by intravitreal injection of 25-mM N-methyl-D-aspartate (NMDA, 2 µL/eye) in GPx4+/+ and GPx4+/- mice. The evaluation of lipid peroxidation (4-HNE immunostaining), apoptosis (TUNEL staining), and cell density in the ganglion cell layer (GCL) were performed at 12 h, 1 day, and 7 days after the NMDA injection. RESULTS: GPx4 knockdown significantly increased LDH activity by 13.9-fold (P < 0.01) and increased peroxidized lipid levels by 3.2-fold in R28 cells (P < 0.01). In cells transfected with scrambled control siRNA, treatment with glutamate at 1 or 2 mM did not increase LDH activity; whereas, in cells transfected with GPx4 siRNA, glutamate treatment significantly increased LDH activity (1.52-fold, P < 0.01). GPx4+/- mice exhibited higher levels of lipid peroxidation in retinas treated with NMDA than GPx4+/+ mice (1.26-fold, P < 0.05). GPx4+/- mice had more TUNEL-positive cells induced by NMDA in GCL (1.45-fold, P < 0.05). In addition, the cell density in GCL of GPx4+/- mice was 19% lower than that in GPx4+/+ mice after treatment with NMDA (P < 0.05). CONCLUSION: These results suggest that defective GPx4 expression is associated with enhanced cytotoxicity by glutamate-induced oxytosis in the retina.

Prevalence of diabetic retinopathy in patients with type 1 diabetes mellitus.

OBJECTIVES: Diabetic retinopathy (DR) is the leading cause of legal blindness in young adults. Scarce data from Brazilian subjects with type 1 diabetes mellitus (DM) are available. AIMS: The objectives of this study were to determine the prevalence of DR and its risk factors in type 1 diabetes mellitus (DM) outpatients from a general hospital. METHODS: A cross-sectional study of 437 type 1 DM (50.3% males, 82.4% whites) was conducted. DR was graded as absent, mild and moderate non-proliferative DR (mild/moderate NPDR) or severe non-proliferative and proliferative DR (advanced DR). Presence of clinically significant macular edema (CSME) was also recorded. RESULTS: Any DR was present in 44.4% of subjects. In multivariate analysis, DM duration, systolic blood pressure (SBP) and A1C test were associated with mild/moderate NPDR (P<0.005). Advanced DR, was associated with DM duration, SBP, smoking [odds ratio (OR) 2.75, 95%CI 1.15-6.60] and micro-or macroalbuminuria (OR 8.53, 95%CI 3.81-18.05). CSME was present in 21 (9.4%) patients and was associated with smoking (OR 3.19, 95%CI 1.24-8.2). Its frequency increased with the severity of DR (16.4% in advanced DR, 9.6% in mild/moderate NPDR, and 4.7% in the group without DR; P = 0.020). CONCLUSION: Patients with type 1 DM attending an endocrine out-patient clinic at a general hospital had a high prevalence of DR associated with traditional risk-factors and smoking.

Prevalence of diabetic retinopathy in patients with type 1 diabetes mellitus / Prevalência de retinopatia diabética em pacientes com diabetes mellitus tipo 1

OBJECTIVES: Diabetic retinopathy (DR) is the leading cause of legal blindness in young adults. Scarce data from Brazilian subjects with type 1 diabetes mellitus (DM) are available. Aims: The objectives of this study were to determine the prevalence of DR and its risk factors in type 1 diabetes mellitus (DM) outpatients from a general hospital. METHODS:A cross-sectional study of 437 type 1 DM (50.3 percent males, 82.4 percent whites) was conducted. DR was graded as absent, mild and moderate non-proliferative DR (mild/moderate NPDR) or severe non-proliferative and proliferative DR (advanced DR). Presence of clinically significant macular edema (CSME) was also recorded. RESULTS: Any DR was present in 44.4 percent of subjects. In multivariate analysis, DM duration, systolic blood pressure (SBP) and A1C test were associated with mild/moderate NPDR (P<0.005). Advanced DR, was associated with DM duration, SBP, smoking [odds ratio (OR) 2.75, 95 percentCI 1.15-6.60] and micro-or macroalbuminuria (OR 8.53, 95 percentCI 3.81-18.05). CSME was present in 21 (9.4 percent) patients and was associated with smoking (OR 3.19, 95 percentCI 1.24-8.2). Its frequency increased with the severity of DR (16.4 percent in advanced DR, 9.6 percent in mild/moderate NPDR, and 4.7 percent in the group without DR; P = 0.020). CONCLUSION: Patients with type 1 DM attending an endocrine out-patient clinic at a general hospital had a high prevalence of DR associated with traditional risk-factors and smoking.

OBJETIVOS: Determinar a prevalência de RD e seus fatores de risco em pacientes com DM tipo 1 atendidos em um hospital geral. MÉTODOS: Foi realizado um estudo transversal com 437 pacientes (50,3 por cento homens, 82,4 por cento brancos). RD foi agrupada em: 1) ausente; 2) não proliferativa leve e moderada (RDNP leve/moderada); 3) não prolifetiva grave e RD proliferativa (RD avançada). Edema de mácula clinicamente significativo (EMCS) também foi registrado. RESULTADOS: Qualquer grau de RD esteve presente em 44,4 por cento dos pacientes. Na análise multivariada, duração do DM, pressão arterial sistólica e teste A1C foram associados com a RD leve/moderada (P<0,005). RD avançada foi associada com duração do DM, pressão arterial sistólica (PAS), fumo [razão de chances (RC) 2,75, IC 95 por cento 1,15-6,60] e micro-ou macroalbuminúria (RC 8,53, CI 95 por cento 3,81-18,05). EMCS esteve presente em 21 (9,4 por cento) dos pacientes associado ao fumo, aumentando com a gravidade da RD (16,4 por cento RD avançada; 9,6 por cento RD leve/modera, e 4,7 por cento no grupo sem RD; P = 0,020). CONCLUSÃO: Pacientes com DM tipo 1 vistos em um hospital geral têm uma alta prevalência de RD, a qual foi associada aos fatores de risco tradicionais e fumo.

[Diabetic retinopathy risk factors]. / Fatores de risco para retinopatia diabética.

Diabetic retinopathy (DR) occurs in about 95% of patients with type 1 diabetes mellitus (DM) and in 60% of type 2 DM patients and it is the main cause of legal blindness in adult people. The aim of this manuscript was to review the main risk factors for DR. The major environmental risk factors are hyperglycemia, high blood pressure levels, and long-term duration of DM. However, not all patients will not develop DR, suggesting the presence of a genetic predisposition to DR, especially for severe forms of DR. Special strategies has been used to evaluate the genetic role in DR. Family studies shown that there is a familial aggregation of DR. Candidates genes have been studied (RAGE; VEGF; PPAR-delta; ICAM-1; ECA; ENPP 1; eNOS) and positive or negative associations with DR were demonstrated. Some chromosomes were also associated to DR in selected populations. Finally, genetic expression studies reinforce the association of candidate genes, or participation of others genes, with the presence of DR. DR is a common complication of DM and, along with non-genetic or environmental risk factors, the identification of genes related to DR could result in more specific and efficient DR treatment.

Fatores de risco para retinopatia diabética: [revisão] / Diabetic retinopathy risk factors: [review]

A retinopatia diabética (RD) acomete cerca de 95 por cento dos pacientes com diabetes melito tipo 1 (DM1) e 60 por cento dos pacientes com diabetes melito tipo 2 (DM2), sendo a principal causa de cegueira legal em adultos. O objetivo desse manuscrito foi revisar os principais fatores de risco para RD. Os fatores de risco ambientais mais importantes são a hiperglicemia sustentada, os valores elevados de pressão arterial e a longa duração de DM. Entretanto, nem todos os pacientes desenvolvem RD, o que sugere a presença de fatores genéticos, em especial para as formas graves de RD. Diferentes estratégias têm sido utilizadas para avaliar o papel da genética na RD. Estudos de famílias demonstraram agregação familiar de RD. Genes candidatos têm sido estudados (RAGE; VEGF; PPAR-delta; ICAM-1; ECA; ENPP 1; eNOS), observando-se associações positivas ou negativas com a RD. Também alguns cromossomos, em populações selecionadas, foram associados à RD. Finalmente, estudos de expressão genética reforçam a associação de genes candidatos, ou determinam a participação de outros, com a presença da RD. A RD é uma complicação freqüente do DM e junto com os fatores não-genéticos ou ambientais, a identificação de genes relacionados à RD poderá resultar tratamentos mais específicos e eficazes para a RD.

Diabetic retinopathy (DR) occurs in about 95 percent of patients with type 1 diabetes mellitus (DM) and in 60 percent of type 2 DM patients and it is the main cause of legal blindness in adult people. The aim of this manuscript was to review the main risk factors for DR. The major environmental risk factors are hyperglycemia, high blood pressure levels, and long-term duration of DM. However, not all patients will not develop DR, suggesting the presence of a genetic predisposition to DR, especially for severe forms of DR. Special strategies has been used to evaluate the genetic role in DR. Family studies shown that there is a familial aggregation of DR. Candidates genes have been studied (RAGE; VEGF; PPAR-delta; ICAM-1; ECA; ENPP 1; eNOS) and positive or negative associations with DR were demonstrated. Some chromosomes were also associated to DR in selected populations. Finally, genetic expression studies reinforce the association of candidate genes, or participation of others genes, with the presence of DR. DR is a common complication of DM and, along with non-genetic or environmental risk factors, the identification of genes related to DR could result in more specific and efficient DR treatment.