Postoperative vision loss due to bilateral vitreous hemorrhage after robot-assisted laparoscopic hysterectomy: A case report.

Purpose: To report a case of bilateral vitreous hemorrhage (VH) resulting in postoperative vision loss (POVL) after robot-assisted laparoscopic hysterectomy in a 71-year-old female patient. Observations: At initial presentation, best-corrected visual acuity was hand motion at 20 cm in the right eye and 20/666 in the left eye. VH in both eyes and preretinal hemorrhage in the left eye was observed. As the hemorrhage gradually resolved, a full-thickness macular hole was discovered in the right eye, for which the patient did not agree with a surgical treatment. Conclusions and importance: This report describes a rare incidence of bilateral VH as a cause of POVL after non-ophthalmic surgery, which may be related to Trendelenburg positioning, CO2 pneumoperitoneum, and a long surgical duration. Given that POVL can cause severe visual impairment, consultation with ophthalmologists is crucial.

Roles of Sphingosine Kinase and Sphingosine-1-Phosphate Receptor 2 in Endotoxin-Induced Acute Retinal Inflammation.

PURPOSE: To investigate the roles of sphingosine kinases (SphKs) and sphingosine-1-phosphate receptors (S1PRs) in endotoxin-induced uveitis (EIU) mice. METHODS: EIU model was induced using an intraperitoneal injection of lipopolysaccharide (LPS). The expression of SphKs and S1PRs in the retina was assessed using quantitative polymerase chain reaction (qPCR) and immunofluorescence. The effects of S1PR antagonists on the expression of inflammatory cytokines in the retina were evaluated using qPCR and western blotting. Effects of leukocyte infiltration of the retinal vessels were evaluated to determine the effects of the S1PR2 antagonist and genetic deletion of S1PR2 on retinal inflammation. RESULTS: Retinal SphK1 expression was significantly upregulated in EIU. SphK1 was expressed in the GCL, IPL, and OPL and S1PR2 was expressed in the GCL, INL, and OPL. Positive cells in IPL and OPL of EIU retina were identified as endothelial cells. S1PR2 antagonist and genetic deletion of S1PR2 significantly suppressed the expression of IL-1α, IL-6, TNF-α, and ICAM-1, whereas S1PR1/3 antagonist did not. Use of S1PR2 antagonist and S1PR2 knockout in mice significantly ameliorated leukocyte adhesion induced by LPS. CONCLUSION: SphK1/S1P/S1PR2 signaling was upregulated in EIU and S1PR2 inhibition suppressed inflammatory response. Targeting this signaling pathway has potential for treating retinal inflammatory diseases.

Macular and peripapillary retinal nerve fiber layer thinning in eyes with prediabetes in the elderly population: OTASSHA study.

PURPOSE: To investigate retinal thickness parameters in the elderly with prediabetes mellitus (preDM) and type 2 DM without retinopathy (non-diabetic retinopathy [NDR]). METHODS: This cross-sectional study included a total of 1273 eyes without retinal pathologies of 699 volunteers aged ≥ 65 years were included. The eyes were categorized into non-DM (606 eyes), preDM (480 eyes), and NDR (187 eyes) groups according to their HbA1c levels. Fundus photography, swept-source optical coherence tomography, and comprehensive systemic examination were conducted. The thicknesses of the retinal nerve fiber layer in the macula (mRNFL) and peripapillary (pRNFL), ganglion cell complex (GCC), and ganglion cell inner plexiform layer (GCIPL), as well as central subfield thickness (CST) and central foveal thickness (CFT) were investigated for their association with DM stage using linear mixed model. RESULTS: A statistically significant thinning of mRNFL was observed in preDM vs. non-DM and in NDR vs. preDM in 3/6 sectors. A significant thinning of pRNFL was observed in preDM vs. non-DM and in NDR vs. preDM in 2/12 sectors. Such DM stage-dependent thinning of RNFL was observed mainly in the temporal and superior sectors. GCIPL and GCC were less sensitive to reflect DM-dependent inner retinal thinning. CST and CFT were not significantly associated with different DM stages. CONCLUSION: The thinning of mRNFL in the temporal and superior sectors might be a sensitive parameter associated with early neurodegeneration in preDM and NDR.

Optical coherence tomography findings after surgery for sub-inner limiting membrane hemorrhage due to ruptured retinal arterial macroaneurysm.

Ruptured retinal arterial macroaneurysm (RAM) can cause sub-inner limiting membrane (ILM) hemorrhage, leading to acute vision loss in the elderly. Vitrectomy has been established as an effective treatment to remove hemorrhage and facilitate visual recovery. Although optical coherence tomography (OCT) is useful for the diagnosis of sub-ILM hemorrhage before surgery, little is known about the postoperative OCT findings. Here, we retrospectively investigated the records of nine eyes of nine patients who underwent surgery for sub-ILM hemorrhage due to RAM rupture. On postoperative OCT, hyperreflectivity throughout the full thickness of the central fovea was observed in eight eyes (88.9%), and disruption of the ellipsoid/interdigitation zone (EZ/IZ) was observed in seven out of eight eyes (87.5%). The widths of the hyperreflectivity and EZ disruption gradually decreased. Visual recovery was least favorable in two eyes, in which the EZ line continuation did not recover until the final follow-up. The OCT findings corresponded to the hemorrhagic staining identified on fundus photographs in at least four eyes; as per the fundus photographs the findings persisted even after the hemorrhage was absorbed. In contrast, the OCT findings resembled the appearance before the development of a full-thickness macular hole, suggesting fragility caused by the RAM rupture.

Mitochondrial glutathione peroxidase 4 is indispensable for photoreceptor development and survival in mice.

Glutathione peroxidase 4 (GPx4) is known for its unique function in the direct detoxification of lipid peroxides in the cell membrane and as a key regulator of ferroptosis, a form of lipid peroxidation-induced nonapoptotic cell death. However, the cytosolic isoform of GPx4 is considered to play a major role in inhibiting ferroptosis in somatic cells, whereas the roles of the mitochondrial isoform of GPx4 (mGPx4) in cell survival are not yet clear. In the present study, we found that mGPx4 KO mice exhibit a cone-rod dystrophy-like phenotype in which loss of cone photoreceptors precedes loss of rod photoreceptors. Specifically, in mGPx4 KO mice, cone photoreceptors disappeared prior to their maturation, whereas rod photoreceptors persisted through maturation but gradually degenerated afterward. Mechanistically, we demonstrated that vitamin E supplementation significantly ameliorated photoreceptor loss in these mice. Furthermore, LC-MS showed a significant increase in peroxidized phosphatidylethanolamine esterified with docosahexaenoic acid in the retina of mGPx4 KO mice. We also observed shrunken and uniformly condensed nuclei as well as caspase-3 activation in mGPx4 KO photoreceptors, suggesting that apoptosis was prevalent. Taken together, our findings indicate that mGPx4 is essential for the maturation of cone photoreceptors but not for the maturation of rod photoreceptors, although it is still critical for the survival of rod photoreceptors after maturation. In conclusion, we reveal novel functions of mGPx4 in supporting development and survival of photoreceptors in vivo.

ASSOCIATION OF PREDIABETES WITH RETINAL MICROVASCULATURE ON SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN THE ELDERLY: OTASSHA Study.

PURPOSE: To investigate the retinal microvasculature in the elderly persons with prediabetes mellitus (preDM) and type 2 DM. METHODS: This cross-sectional study included a total of 452 eyes without retinal pathologies of 301 elderly volunteers aged ≥65 years, and they were categorized into nonDM (225 eyes), preDM (177 eyes), and DM (50 eyes) groups based on their HbA1c. Fundus photography, swept-source optical coherence tomography and angiography, and comprehensive systemic examinations were conducted. Vessel density (VD) and foveal avascular zone in superficial and deep retinal microvasculature were investigated for their association with DM stages using linear mixed model. RESULTS: Superficial VD (sVD) mean values in nonDM, preDM, and DM groups were 35.2%, 34.9%, and 34.8%, respectively. sVD in preDM was equivalent to sVD in DM, whereas significantly lower compared with sVD in nonDM (difference [95% CI] -0.19 [-0.33 to -0.049], P = 0.009). Deep VD (dVD) mean values in nonDM, preDM, and DM groups were 35.0%, 35.0%, and 34.4%, respectively. dVD in preDM was equivalent to dVD in nonDM, whereas significantly higher compared with dVD in DM (difference [95% CI] 0.31 [0.046-0.57], P = 0.02). There was no significant association between foveal avascular zone area and DM stages. CONCLUSION: Retinal microvasculature may be affected at the prediabetic stage in the elderly.

Surgical Treatment for a Full-Thickness Macular Hole That Developed on a Large Drusenoid Pigment Epithelial Detachment.

Full-thickness macular hole (FTMH) and age-related macular degeneration (AMD) can affect the same eyes in the older population. Previously reported phenotypes of AMD concurrent with FTMH include early/intermediate AMD and serous pigment epithelial detachment (PED). A 68-year-old woman presented to our clinic with decreased vision due to a cataract and a large drusenoid PED in both eyes. After ruling out choroidal neovascularization, she underwent cataract surgery. Three days after the cataract surgery, an FTMH was found in the left eye. Although the FTMH was not closed after the initial pars plana vitrectomy (PPV) with the inner limiting membrane (ILM) peeling and air tamponade, it was closed after reoperation with additional ILM peeling, retinal massage, and SF6 gas tamponade. Best-corrected visual acuity (BCVA) was improved from 20/60 before the first PPV to 20/40 at six months after the reoperation. Some large soft drusen in the macula were fused after surgeries in the operated eye, but not in the fellow eye. An FTMH concurrent with a large drusenoid PED is rare. It can be closed surgically, and postoperative visual function can improve.

Fovea-Sparing as Opposed to Total Peeling of Internal Limiting Membrane for Myopic Foveoschisis: A Systematic Review and Meta-analysis.

TOPIC: The effectiveness of fovea-sparing (FS) peeling of internal limiting membrane (ILM) to treat myopic foveoschisis (MF) has not been understood fully. The present meta-analysis aimed to compare postoperative visual and anatomic outcomes between FS peeling and total peeling (TP) of ILM in pars plana vitrectomy for the treatment of MF. CLINICAL RELEVANCE: Postoperative macular hole (MH) development is not uncommon and is a serious complication after surgery for MF, with poor visual prognosis. Fovea-sparing peeling of ILM is expected to reduce the risk of postoperative MH; however, no statistically significant evidence exists to prove this hypothesis. In addition, its effect on postoperative visual acuity has not been clear. METHODS: MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and EMBASE were reviewed systematically, and studies that compared FS with total ILM peeling in MF surgery were retrieved. The protocol was registered in International Prospective Register of Systematic Reviews (identifier, CRD42020201675). Primary outcome measures were the postoperative best-corrected visual acuity (BCVA) and frequency of postoperative MH development. Certainty of evidence was evaluated by the Grading of Recommendations Assessment, Development and Evaluation system. RESULTS: Eight studies with 300 eyes from 289 patients were included. All studies were nonrandomized and observational. The postoperative BCVA was significantly better in eyes treated with FS (mean difference [MD], -0.15 logarithm of the minimum angle of resolution [logMAR]; 95% confidence interval [CI], -0.24 to -0.05 logMAR; P = 0.002). The risk of postoperative MH was significantly lower in the FS group (odds ratio, 0.19; 95% CI, 0.06-0.56; P = 0.003). No significant difference was found in postoperative central foveal thickness (MD, 12.59 µm; 95% CI, -2.8 to 28.0 µm; P = 0.11). The certainty of evidence regarding lower frequency of postoperative MH after FS peeling was considered moderate, whereas the certainty regarding better postoperative BCVA after FS peeling was judged to be low. DISCUSSION: Fovea-sparing peeling may contribute to better visual acuity outcome and lower risk of postoperative MH development in eyes with MF.

Comparison between blue-on-yellow and white-on-white perimetry in patients with branch retinal vein occlusion.

This study aimed to compare blue-on-yellow (B/Y) perimetry with white-on-white (W/W) perimetry in eyes with branch retinal vein occlusion (BRVO). The following measurements were performed in 29 eyes of 29 patients with resolved BRVO: W/W and B/Y perimetries using 10-2 test grid, retinal volume (RV) using optical coherence tomography (OCT), and vessel densities (VD) of the superficial capillary layer (VDs) and deep capillary layer (VDd) using OCT angiography (OCTA). First, the difference in the retinal sensitivity (RS) between BRVO-affected and unaffected areas was compared between RS_B/Y and RS_W/W in the parafoveal and extrafoveal areas. Moreover, the structure-function relationship between vessel density and RS was compared between B/Y and W/W perimetries (RS_B/Y and RS_W/W, respectively). The difference in RS between BRVO-affected and unaffected areas was significantly larger with RS_B/Y than with RS_W/W in both the parafoveal and extrafoveal areas. In the parafoveal area, VDs, VDd, and RV were significantly correlated with both RS_W/W and RS_B/Y. In contrast, in the extrafoveal area, only VDd was included in the optimal models. Our findings suggest that RS_B/Y more strongly reflects the anatomical structure and BRVO-affected area.

Continued smoking and posterior vitreous adhesion in the elderly evaluated on swept-source optical coherence tomography.

In this cross-sectional study including 1150 eyes of 681 volunteers ≧ 65 years old without retinal pathology, factors affecting the progression of posterior vitreous detachment (PVD) were investigated. PVD stages were diagnosed based on swept-source optical coherence tomography (SS-OCT). Linear mixed effect model was used to determine whether age, gender, diabetes mellitus (DM), hypertension (HT), dyslipidemia (DL), and smoking status were associated with various stages of PVD. As a result, the multivariable analysis disclosed that the associations between older age and higher PVD stages (estimate [95% CI], 0.031 [0.020 to 0.042]; P < 0.0001), and current smokers and lower PVD stages (estimate [95% CI], - 0.24 [- 0.43 to - 0.056]; P = 0.011) were statistically significant. In contrast, female gender was not an independent factor affecting PVD stages in the elderly. Our analysis indicated that higher PVD stages observed in female eyes may be due to confounding effect, in which current smokers were predominantly males (i.e., 12.6% among males vs. 3.9% among females, P < 0.0001). In conclusion, our findings suggest that continuous smoking is associated with an adherent vitreoretinal interface in the elderly.

A Prediction Method of Visual Field Sensitivity Using Fundus Autofluorescence Images in Patients With Retinitis Pigmentosa.

Purpose: The purpose of this study was to investigate the association between fundus autofluorescence (FAF) and visual field (VF) sensitivities in eyes with retinitis pigmentosa (RP). We also investigated the model we developed to predict VF sensitivity using the FAF ring and its prediction accuracy. Methods: The training dataset consisted of 51 eyes of 28 patients, and the testing dataset consisted of 42 eyes of 25 patients with RP. VF and FAF measurements were conducted using the Humphrey Field Analyzer (HFA) 10-2 test and Optos. The HFA 10-2 test was divided into three sectors according to the association with the FAF (IN, ON, and OUT). Moreover, concentric curves were drawn at 1-degree intervals outside the FAF ring and OUT was divided into six sectors (from OUT1 to OUT6 toward the periphery). Finally, the total deviation (TD) value was predicted using age and visual acuity (VA) in the whole field, and each of the eight sectors was compared. Results: The TD value decreased significantly from IN, ON, and then toward OUT6. The absolute prediction error with the FAF ring (average, 7.6 dB) was significantly smaller than that without the FAF ring (average, 8.7 dB). The absolute prediction error with the FAF ring was significantly smaller in the central areas (IN, 4.4 dB and ON, 5.3 dB) than those in the peripheral areas (OUT1-6, 6.8-9.1 dB). Conclusions: VF sensitivity decreases in association with the FAF ring. We developed a model to predict 10-2 VF sensitivity values using the FAF ring, which enabled us to predict 10-2 TD values.

Frequency of hypotonic maculopathy observed by spectral domain optical coherence tomography in post glaucoma filtration surgery eyes.

PURPOSE: To report the frequency of post glaucoma filtration surgery hypotonic maculopathy determined by spectral domain optical coherence tomography (SD-OCT). METHODS: A cross-sectional retrospective observational study. Post glaucoma filtration surgery patients whose intraocular pressures (IOP) achieved 30% reduction from baseline or was controlled to IOP <14 mm Hg and had SD-OCT images and fundus photographs were enrolled. Hypotonic maculopathy was diagnosed independently on SD-OCT images and on fundus photographs. RESULTS: 112 eyes of 88 patients were included in this study. 17 eyes of 14 patients were diagnosed with hypotonic maculopathy on SD-OCT images (17/112, 15.2%). Among these eyes, only 3 eyes were also diagnosed with hypotony maculopathy on fundus photography. Hypotonic maculopathy on SD-OCT was found only in eyes with IOP ≤10 mm Hg. (17.4% in eyes with IOPs between 7 and 10 mm Hg, and 22.7% in eyes with IOP ≤ 6 mm Hg). Associations with age, sex, central corneal thickness, refractive error, IOP reduction rate and interval between surgery and OCT acquisition were not significant (P > 0.05). CONCLUSION: In most cases, hypotonic maculopathy detected by SD-OCT were not recognizable on fundus photographs. Hypotonic maculopathy was detected not only in eyes with conventional ocular hypotony (IOP < 6 mm Hg) but also in eyes with IOP between 7 and 10 mm Hg.

Association between pachychoroid and long-term treatment outcomes of photodynamic therapy with intravitreal ranibizumab for polypoidal choroidal vasculopathy.

We investigated long-term treatment responses in patients with treatment-naïve polypoidal choroidal vasculopathy (PCV) undergoing photodynamic therapy (PDT) with intravitreal ranibizumab (IVR). The medical charts of 14 patients with treatment-naïve PCV who underwent PDT with IVR were retrospectively reviewed. Patients were followed up and treated with additional IVR for ≥3 years. Best-corrected visual acuity (BCVA), central foveal thickness (CFT), greatest linear dimension (GLD) on angiography, polyp regression and central choroidal thickness (CCT) were assessed. Associations between these functional or anatomic outcomes with age, baseline CCT, baseline GLD or choroidal vascular hyperpermeability (CVH) were investigated using univariate and multivariate analysis. Mean logMAR BCVA improved significantly at 3 years (0.34 ± 0.24 to 0.12 ± 0.29, p = 0.003). Greater BCVA improvement and longer time to first recurrence was significantly associated with CVH. Fewer number of IVR retreatment within 3 years was associated with thicker baseline CCT. Mean CCT significantly decreased at 3 years (217 ± 33 µm to 197 ± 48 µm, p = 0.003). Greater decrease of CCT was significantly associated both with greater number of IVR retreatment within 3 years and absence of CVH. These results showed that pachychoroid characteristics at baseline was associated long-term functional and anatomic outcomes in patients with treatment-naïve PCV who had undergone combination PDT and IVR.

RIP1 kinase mediates angiogenesis by modulating macrophages in experimental neovascularization.

Inflammation plays an important role in pathological angiogenesis. Receptor-interacting protein 1 (RIP1) is highly expressed in inflammatory cells and is known to play an important role in the regulation of apoptosis, necroptosis, and inflammation; however, a comprehensive description of its role in angiogenesis remains elusive. Here, we show that RIP1 is abundantly expressed in infiltrating macrophages during angiogenesis, and genetic or pharmacological inhibition of RIP1 kinase activity using kinase-inactive RIP1K45A/K45A mice or necrostatin-1 attenuates angiogenesis in laser-induced choroidal neovascularization, Matrigel plug angiogenesis, and alkali injury-induced corneal neovascularization in mice. The inhibitory effect on angiogenesis is mediated by caspase activation through a kinase-independent function of RIP1 and RIP3. Mechanistically, infiltrating macrophages are the key target of RIP1 kinase inhibition to attenuate pathological angiogenesis. Inhibition of RIP1 kinase activity is associated with caspase activation in infiltrating macrophages and decreased expression of proangiogenic M2-like markers but not M1-like markers. Similarly, in vitro, catalytic inhibition of RIP1 down-regulates the expression of M2-like markers in interleukin-4-activated bone marrow-derived macrophages, and this effect is blocked by simultaneous caspase inhibition. Collectively, these results demonstrate a nonnecrotic function of RIP1 kinase activity and suggest that RIP1-mediated modulation of macrophage activation may be a therapeutic target of pathological angiogenesis.

EFFECTS OF INTERNAL LIMITING MEMBRANE PEELING COMBINED WITH REMOVAL OF IDIOPATHIC EPIRETINAL MEMBRANE: A Systematic Review of Literature and Meta-Analysis.

PURPOSE: To evaluate the effects on postoperative prognosis of internal limiting membrane (ILM) peeling in conjunction with removal of idiopathic epiretinal membranes (ERMs). METHODS: MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and EMBASE were systematically searched for studies that compared ILM peeling with no ILM peeling in surgery to remove idiopathic ERM. Outcome measures were best-corrected visual acuity, central macular thickness, and ERM recurrence. Studies that compared ILM peeling with no ILM peeling for the treatment of idiopathic ERM were selected. RESULTS: Sixteen studies that included 1,286 eyes were selected. All the included studies were retrospective or prospective comparative studies; no randomized controlled study was identified. Baseline preoperative best-corrected visual acuity and central macular thickness were equal between ILM peeling and no ILM peeling groups. Postoperatively, there was no statistically significant difference in best-corrected visual acuity (mean difference 0.01 logarithm of the minimum angle of resolution [equivalent to 0.5 Early Treatment Diabetic Retinopathy Study letter]; 95% CI -0.05 to 0.07 [-3.5 to 2.5 Early Treatment Diabetic Retinopathy Study letters]; P = 0.83) or central macular thickness (mean difference 13.13 µm; 95% CI -10.66 to 36.93; P = 0.28). However, the recurrence rate of ERM was significantly lower with ILM peeling than with no ILM peeling (odds ratio 0.25; 95% CI 0.12-0.49; P < 0.0001). CONCLUSION: Currently available evidence in the literature indicates that additional ILM peeling in vitrectomy for idiopathic ERM could result in a significantly lower ERM recurrence rate, but it does not significantly influence postoperative best-corrected visual acuity and central macular thickness.

BRILLIANT BLUE G-ASSISTED INTERNAL LIMITING MEMBRANE PEELING FOR MACULAR HOLE: A Systematic Review of Literature and Meta-Analysis.

PURPOSE: To evaluate the effect of internal limiting membrane peeling with brilliant blue G (BBG) for the treatment of macular hole compared with peeling procedures with other dyes or without dye. METHODS: MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) were systematically reviewed. Outcome measures were the primary closure rate and postoperative best-corrected visual acuity. RESULTS: Nine studies that included 846 eyes were selected. There was no significant difference in preoperative best-corrected visual acuity between the BBG and no BBG (i.e., other dyes or no dye) groups (mean difference -0.02 logMAR [equivalent to 1 Early Treatment Diabetic Retinopathy Study (ETDRS) letter]; 95% confidence interval -0.09 to 0.04 [-2-4.5 ETDRS letters]; P = 0.45). The macular hole closure rate using BBG was not significantly different from that using indocyanine green (odds ratio 1.98; 95% confidence interval 0.71-5.48; P = 0.19). The postoperative best-corrected visual acuity was more favorable with BBG than with indocyanine green (mean difference -0.10 logMAR [5 ETDRS letters]; 95% confidence interval -0.16 to -0.03 [1.5-8 ETDRS letters]; P = 0.004) or with no BBG (mean difference -0.11 [5.5 ETDRS letters]; 95% confidence interval -0.18 to -0.04 [2-9 ETDRS letters]; P = 0.003). CONCLUSION: BBG could contribute to better visual acuity outcome than other dyes for internal limiting membrane peeling in patients with macular hole; however, it does not significantly influence the closure rate.