PREDICTION OF DIABETIC RETINOPATHY SEVERITY USING A COMBINATION OF RETINAL NEURODEGENERATION AND CAPILLARY NONPERFUSION ON OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To generate a prediction model of diabetic retinopathy (DR) severity stages based on retinal neurodegeneration and capillary nonperfusion area (NPA) detected using optical coherence tomography (OCT) and OCT angiography (OCTA). METHODS: A total of 155 treatment-naïve eyes were retrospectively included. Macular ganglion cell/inner plexiform layer (mGCIPL) thickness in six macular regions was measured. A custom algorithm was used to calculate capillary NPA from 3 × 3 mm 2 and 12 × 12 mm 2 field OCTA images. The region of interest was selected as circular areas of 3 mm and 12 mm diameter and divided into six subsections. Classification and regression tree analysis identified the best predictors to discriminate between the five DR stages. RESULTS: Inferotemporal sector showed the largest mean NPA, and the inferior hemispheric NPA was significantly larger compared with the superior hemisphere. The mean mGCIPL thickness was significantly correlated with NPA of 12 × 12 mm 2 field in participants with early stage DR. Inferior hemispheric NPA of 12 × 12 mm 2 field and mean mGCIPL thickness were the two best variables to discriminate no DR versus mild nonproliferative DR (NPDR) and mild versus moderate NPDR (accuracy: 88.8% and 93.5%). Meanwhile, a combination of NPA of 12 × 12 mm 2 and 3 × 3 mm 2 fields was the best prediction model to discriminate moderate versus severe NPDR and severe NPDR versus PDR (accuracy: 91.8% and 94.1%). CONCLUSION: A combination model of capillary NPA and mGCIPL thickness may be a novel biomarker for predicting DR severity. Capillary nonperfusion seems to initially occur in the midperipheral retina with macular neurodegeneration and progress posteriorly.

Seven-year outcomes of combined treatment of anti-vascular endothelial growth factor with photodynamic therapy for polypoidal choroidal vasculopathy; according to polypoidal lesion regression.

PURPOSE: To evaluate the long-term prognosis of polypoidal choroidal vasculopathy (PCV) treated with anti-vascular endothelial growth factor (anti-VEGF) combined with verteporfin photodynamic therapy (PDT), according to polypoidal lesion regression. METHODS: This study retrospectively reviewed the data of 33 naïve eyes with PCV treated with anti-VEGF combined with verteporfin PDT and followed-up for at least 7 years. The collected data included demographic profile, best-corrected visual acuity (BCVA), central foveal thickness (CFT), PED volume, and presence of submacular hemorrhage. Regression of polypoidal lesion was determined using indocyanine green angiography and optical coherence tomography. All eyes were divided into regression or persistent groups, based on the polypoidal lesion regression one year after the initial combined treatment. RESULTS: BCVA improvement was maintained for 3 years in the regression (p = 0.001) and 1 year in the persistent (p = 0.006) groups, respectively. The mean BCVA of the regression group was better than that of the persistent group over 7 years, but the difference was significant only at 1 year (p = 0.037). The number of eyes which maintained BCVA less than or equal to 0.3 logMAR at 7 years was 11 eyes (64.7%) in regression group and 4 eyes (25.0%) in persistent group (p = 0.022). CONCLUSIONS: Regression of the polypoidal lesion at 1 year after the initial combination treatment was associated with favorable long-term visual prognosis, particularly in terms of maintaining good visual acuity.

Peripapillary microvasculature changes after vitrectomy in epiretinal membrane via swept-source OCT angiography.

PURPOSE: To evaluate the peripapillary microvasculature changes in patients with epiretinal membrane (ERM) following pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling using swept-source optical coherence tomography angiography (SS-OCTA). METHOD: Medical records and multimodal imaging data of 33 eyes after PPV for ERM were retrospectively reviewed. Peripapillary SS-OCTA images of 6×6 mm2 were recorded at at pre- and post-operatively every 6 months for 1 year. A semi-automated method was used to analyzed SS-OCTA images, excluding the optic disc area, using the MATLAB software. The peripapillary vessel density (pVD) of superficial capillary plexus (SCP) and deep capillary plexus (DCP) was quantified in four quadrants (superior, inferior, nasal and temporal). RESULT: The mean pVD in SCP and DCP decreased at 6- and 12-months follow-up. In sectoral analysis, superior, inferior, and temporal quadrants pVD in SCP and DCP were significantly reduced at 1 year after vitrectomy (all p < 0.05). Meanwhile, inferior quadrants pVD in SCP and DCP showed the earliest significant reduction at 6-months (p = 0.022 and 0.048, respectively). A reduction of post-operative mean pVD in DCP was significantly greater in patients with diabetic retinopathy (p = 0.043). CONCLUSION: Peripapillary capillary density significantly decreased after surgical removal of ERM. Vitrectomy with ILM peeling can cause peripapillary microvascular damage starting in inferior sector.

Optical coherence tomography angiography biomarkers in a bi-monthly maintenance dosing aflibercept in patients with neovascular age-related macular degeneration.

PURPOSE: To evaluate the correlations between swept-source optical coherence tomography angiography (SS-OCTA) parameters and clinical outcomes in eyes with neovascular age-related macular degeneration (nAMD) administered a bimonthly intravitreal aflibercept regimen. METHODS: This prospective, single-arm, interventional study enrolled 33 patients with treatment-naïve nAMD. The eyes received three monthly aflibercept injections followed by five bi-monthly regimens (total 50 weeks). The structural parameters including central subfield thickness (CST) and 5 mm pigment epithelial detachment (PED) volume and microvascular parameters including macular neovascularization (MNV) area, vessel density (VD), and vessel length density (VLD) were recorded every before and 1 week after treatment. RESULTS: Patients who gained > 5 letters of best-corrected visual acuity (BCVA) from the baseline showed greater decreases in VD and VLD during the loading phase. Patients without recurrent or persistent fluid during the maintenance phase showed greater decreases in CST and 5 mm PED volume after the first injection. The decrease in mean VD during the loading phase was significantly correlated with the final BCVA (r = -0.820, p = 0.004). Moreover, the decrease in mean VLD during the loading phase was significantly correlated with the improvement in the final BCVA (r = -0.726, p = 0.017). CONCLUSIONS: The decrease in mean VD during the loading phase was significantly negatively correlated with the final BCVA at the last visit. The decrease in mean VLD during the loading phase, mean CST during the loading phase, and the improvement in final BCVA showed significant correlations. Therefore, early changes in OCTA microvascular and OCT structural parameters could help predict clinical outcomes in nAMD. TRIAL REGISTRATION: The trial was registered with the Clinical Research Information Service (CRIS), which joined the WHO International Clinical Trials Registry Platform (ICTRP) (Registration number: KCT0007375, Date of first trial registration: 10/06/2022).

Perifoveal Microvascular Changes following Internal Limiting Membrane Peeling Surgery for Epiretinal Membrane and Macular Hole.

INTRODUCTION: The aim of the study was to evaluate perifoveal microvasculature changes following pars plana vitrectomy with internal limiting membrane peeling for the epiretinal membrane (ERM) and macular hole (MH). METHODS: This retrospective study included 59 eyes from 59 patients. Subjects were divided into two groups: an ERM group (n = 43) and an MH group (n = 16) based on the initial diagnosis. Swept-source optical coherence tomography angiography (SS-OCTA) was performed in the macular area, pre- and postoperatively. Perifoveal microvascular changes were calculated using MATLAB from the 6 × 6 mm SS-OCTA images, excluding the foveal avascular zone. Pre- and postoperative perifoveal vessel densities (pfVDs) were separately analyzed in six sectors (superior, superotemporal, inferotemporal, inferior, inferonasal, and superonasal) in the superficial capillary plexus (SCP) and deep capillary plexus (DCP). The baseline characteristics and other clinical factors were compared between the ERM and MH groups. RESULTS: The postoperative best-corrected visual acuity significantly improved in both groups (p < 0.05). One year after surgery, the pfVD in the SCP of the ERM group significantly decreased in the inferotemporal sector (p = 0.049). The postoperative pfVD in the DCP of the MH group significantly decreased in temporal sectors (p < 0.05). The postoperative mean pfVD in the SCP in the MH group was significantly lower than that in the ERM group (p = 0.003). The presence of a dissociated optic nerve fiber layer (DONFL) was 75% in the MH group and 22% in the ERM group (p = 0.018). The correlation between the pfVD and DONFL was not statistically significant. CONCLUSION: Postoperative pfVD reduction in the temporal sector, a corresponding area in which DONFL is present after MH surgery, was significantly observed. After vitreoretinal surgery in MH patients, OCTA may serve as a useful tool for monitoring perifoveal microvascular changes, especially in temporal sectors.

Quantification of retinal microvascular parameters by severity of diabetic retinopathy using wide-field swept-source optical coherence tomography angiography.

PURPOSE: To investigate the diagnostic utility of microvascular parameters for grading the severity of diabetic retinopathy (DR) with a range of views using wide-field swept-source optical coherence tomography angiography (SS-OCTA). METHODS: This retrospective study grouped 235 eyes with diabetes into the five grades: diabetes without retinopathy (no-DR), mild non-proliferative DR (NPDR), moderate NPDR, severe NPDR, and proliferative DR (PDR). Foveal avascular zone (FAZ) metrics, vessel density (VD), and the capillary nonperfusion area (NPA) were quantified with a customized, semiautomatic software algorithm. Regions of interest were selected from three rectangular fields of different sizes (i.e., 3 × 3 mm2, 6 × 6 mm2, and 10 × 10 mm2), perpendicular to the fovea-optic disc axis. RESULTS: NPA obtained from the 6 × 6mm2 and 10 × 10mm2 areas was the only discriminating parameter for the three NPDR stages. ROC curve analysis revealed that NPA from the 10 × 10mm2 field exhibited the best performance for grading DR into five stages. The NPA cutoff values were 3.7% (area under the curve (AUC): 0.91), 4.7% (AUC: 0.94), 9.3% (AUC: 0.94), and 21.4% (AUC: 0.90) for grading no-DR, mild from moderate NPDR, moderate from severe NPDR, and severe NPDR from PDR, respectively. CONCLUSIONS: Increasing DR severity as assessed by conventional grading systems is accompanied with increasing retinal ischemia on SS-OCTA. NPA measured from the larger 10 × 10 mm2 scan area showed the highest sensitivity for determining five-grade DR severity. In the future, the addition of quantitative NPA may provide a more clinically feasible DR grading system.

GAP IN CAPILLARY PERFUSION AND BURDEN OF TREATMENT IN BRANCH RETINAL VEIN OCCLUSION: A Wide-Field Optical Coherence Tomography Angiography Study.

PURPOSE: To evaluate correlations between the burden of antivascular endothelial growth factor treatment and microperfusion status in superficial capillary plexus and deep capillary plexus (SCP and DCP) using wide-field optical coherence tomography angiography. METHODS: A total 19 eyes with branch retinal vein occlusion were included in this retrospective study. Area of foveal avascular zone, capillary nonperfusion area, vascular density, and perfusion gap were compared between superficial capillary plexus and DCP. Internal areas of 3, 6, and 12 mm in diameter around the fovea were analyzed separately. RESULTS: The mean number of injections per months was 0.20 ± 0.12. The number of antivascular endothelial growth factor injections per month showed a significant correlation with perfusion gap in 12 mm area (P = 0.010), but not with perfusion gap in 3-mm or 6-mm area. Correlations were also found between the final best-corrected visual acuity and vascular density in the 12 mm area of DCP (P = 0.031) and foveal avascular zone area (P = 0.033). CONCLUSION: Wide-field optical coherence tomography angiography is very useful for assessing the microperfusion status in branch retinal vein occlusion. In extended field of view (12 mm × 12 mm), a larger perfusion gap was associated with frequent requirements of antivascular endothelial growth factor injections for macular edema. Reduction in vessel density was significantly correlated with poor visual outcome.

Longitudinal Microvascular Changes on Optical Coherence Tomographic Angiography after Macula-Off Rhegmatogenous Retinal Detachment Repair Surgery.

PURPOSE: To investigate longitudinal changes and associated factors for microvascular parameters in macula-off rhegmatogenous retinal detachment (RRD) after repair surgery. METHODS: This is a retrospective study of 34 eyes with macula-off RRD. The foveal avascular zone (FAZ) area and parafoveal vessel density were recorded every 3 months for 1 year after surgery. We analyzed 3 × 3 mm and 6 × 6 mm swept-source optical coherence tomographic (OCT) angiography images to quantify microvascular parameters. Individual clinical factors and pre- and postoperative OCT images were analyzed to find factors associated with changes in the FAZ area and vessel density 12 months after surgery. RESULTS: The differences in FAZ area and vessel density between the operated and fellow eye at 3, 6, 9, and 12 months postoperatively were 0.127 ± 0.05, 0.111 ± 0.06, 0.108 ± 0.07, and 0.105 ± 0.06 mm2 and 4.33 ± 1.42, 3.56 ± 2.05, 2.73 ± 1.72, and 2.61 ± 1.71/mm. Preoperative sensory retina thickness and surgical methods significantly correlated with decreased vessel density at 12 months. Surgical method-based analysis found that postoperative vessel density damage in the pars plana vitrectomy (PPV) group was more prominent than in the buckling group. CONCLUSION: After macula-off RRD surgery, microvascular parameters were impaired after successful anatomical repair but recovered over 12 months. The PPV group exhibited significantly lower postoperative parafoveal vessel density than the buckling group.

Automatic segmentation of corneal dystrophy on photographic images based on texture analysis.

PURPOSE: To develop an automatic algorithm to analyze dystrophic lesions on photographic images of corneal dystrophy. METHODS: The dataset included 32 images of corneal dystrophy. The dystrophic area was manually segmented twice. Manually labeled dystrophy areas were compared with automatically segmented images. First, we manually removed the light reflex from the image of the cornea. Using an automatic approach, we extracted the brown color of the iris. Then, the program detected the circular region of the pupil and the corneal surface. A whitish dystrophy area was defined based on the image intensity on the iris and the pupil. The sliding square kernel was applied to clearly define the dystrophic region. RESULTS: For the manual analysis and the twice automatic approach, the Dice similarity was 0.804 and 0.801, respectively. The Pearson correlation coefficient was 0.807 and 0.806, respectively. The total number of distinct dystrophic areas showed no significant difference between the manual and automatic approaches according to the Wilcoxon signed-rank test (p < 0.0001, both). CONCLUSIONS: We proposed an automatic algorithm for detecting the dystrophy areas on photographic images with an accuracy of approximately 0.80. This system can be applied to detect and predict the progression of corneal dystrophy.

FUNDUS AUTOFLUORESCENCE PATTERNS IN CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: To investigate the patterns of fundus autofluorescence (FAF) abnormalities in patients with central serous chorioretinopathy (CSC). METHODS: This cross-sectional observational study included 126 eyes of 118 patients who were diagnosed with central serous chorioretinopathy from December 2006 to April 2012 at Kyung Hee University Hospital, Seoul, Korea. Fundus autofluorescence patterns were analyzed with spectral domain optical coherence tomography and visual acuity. RESULTS: Fundus autofluorescence patterns were grouped as blocked (38.9%), mottled (8.7%), hyper (31.0%), hyper/hypo (13.5%), or descending tract (8.0%). The duration of symptoms was 7.8 (±20.4), 28.3 (±31.8), 42.5 (±69.1), 163.8 (±183.5), and 174.5 (±162.3) days in the blocked, mottled, hyper, descending tract, and hyper/hypo groups, respectively (P < 0.001). The blocked FAF group had the best visual acuity (P = 0.011). The intact ellipsoid zone on the spectral domain optical coherence tomography was mostly found in the blocked FAF group (P < 0.001), and the disrupted ellipsoid zone was commonly exhibited in the hyper/hypo and descending tract groups. Disrupted external limiting membrane line on the spectral domain optical coherence tomography was seen in two patients of the descending tract group only. CONCLUSION: The FAF abnormalities in central serous chorioretinopathy show multiple patterns and are related with the chronicity and visual acuity. Fundus autofluorescence patterns in central serous chorioretinopathy are helpful when considering the timing of treatment and predicting the disease status.

Five-Year Follow-Up of Unaffected Fellow Eyes in Patients with Polypoidal Choroidal Vasculopathy.

PURPOSE: To evaluate the incidence and risk factors of neovascular age-related macular degeneration (nAMD) including polypoidal choroidal vasculopathy (PCV) or any type of choroidal neovascularization (CNV) in fellow eyes of unilateral PCV. METHODS: This retrospective study included 48 patients with unilateral PCV. For the initial PCV diagnosis, optical coherence tomography and indocyanine green angiography were performed, and patients with and without neovascularization were compared. RESULTS: Of 48 fellow eyes, 10 (20.8%) had drusen, 9 (18.8%) had retinal pigment epitheliopathy, 9 (18.8%) had irregular retinal pigment epithelium (RPE) elevation, 13 (27.1%) had choroidal vascular dilation, 12 (25%) had choroidal vascular hyperpermeability, and 9 (18.8%) had branching vascular network (BVN) at baseline. The development of nAMD was noted in 8 eyes (17%). The subfoveal choroidal thickness (p = 0.001), irregular RPE elevation (p < 0.001), choroidal vascular dilation (p < 0.001), choroidal vascular hyperpermeability (p < 0.001), and BVN (p < 0.001) in fellow eyes were significantly correlated with development of PCV. After multivariate analysis, BVN (p = 0.045, odds ratio = 24.66) in the fellow eye was the only significant risk factor for the development of nAMD. CONCLUSIONS: PCV or CNV developed in 17% of fellow eyes during the 5 years. Unilateral PCV with contralateral BVN requires careful monitoring for future development of PCV or CNV in fellow eyes.

Central serous chorioretinopathy in elderly subjects: angiographic and tomographic characteristics.

PURPOSE: To investigate the angiographic, tomographic, and clinical characteristics of idiopathic central serous chorioretinopathy (CSC) in elderly patients. METHODS: The patients were divided into two groups according to a cutoff age of 60 years at baseline. Patients underwent spectral domain optical coherence tomography, fluorescein angiography, and indocyanine green angiography. Angiographic and tomographic features were compared between the two groups (young vs. elderly group). RESULTS: Of 176 patients, 26 patients (15.1%) were 60 years or older. Complete resolution of subretinal fluid after treatment was noted in 72.0% of the elderly group and 90.8% of the young group (P = 0.021). The elderly group showed worse baseline and final vision, more bilateral involvement, and lower male preponderance than the young group (P < 0.05, respectively). The elderly group was also associated with a higher frequency of retinal pigment epithelium depigmentation, foveal thinning, and double-layer sign compared with the young group (P < 0.05, respectively). CONCLUSION: CSC in elderly patients was associated with a lower resolution of serous detachment, increased impairment of retinal pigment epithelial layers, foveal thinning, and worse visual outcome, suggesting a chronic insult to the choroidal vessels involving more severe damage to the outer retinal layers.

OUTCOME OF INTRAVITREAL AFLIBERCEPT FOR REFRACTORY PIGMENT EPITHELIAL DETACHMENT WITH OR WITHOUT SUBRETINAL FLUID AND SECONDARY TO AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To investigate the outcomes of intravitreal aflibercept in refractory pigment epithelial detachment (PED) with or without subretinal fluid (SRF) in patients with neovascular age-related macular degeneration. METHODS: A prospective, nonrandomized, interventional case series involved 40 patients with persistent vascularized PED previously treated with at least 3 injections of intravitreal bevacizumab or ranibizumab. Intravitreal aflibercept was administered as 3 initial loading doses every 4 weeks, followed by pro re nata retreatment every 8 weeks over 48 weeks. Pigment epithelial detachment was classified into solid-, hollow-, or mixed-type according to the reflective properties visualized using optical coherence tomography. The mean changes in best-corrected visual acuity, central subfield thickness, and the volumes of SRF and PED were analyzed. RESULTS: The PED volume (baseline: 0.43 ± 0.55 mm) significantly reduced to 0.23 ± 0.32 mm at Week 8 (P = 0.003) and increased to 0.36 ± 0.41 mm at Week 48 (P = 0.345). The SRF volume (baseline: 0.52 ± 0.64 mm) significantly reduced to 0.24 ± 0.43 mm at Week 48 (P = 0.021). The mean baseline best-corrected visual acuity was 20/75 (47.5 letters); it showed no significant difference at Week 48 (+4.4 letters; P = 0.125). The baseline central subfield thickness was 323.2 ± 92.3 µm; it significantly reduced to 281.2 ± 90.7 µm at Week 48 (P = 0.001). In solid-type PEDs, there were poorer improvements in central subfield thickness, best-corrected visual acuity, and the volumes of the SRF and PED, with newly developed intraretinal cysts. CONCLUSION: Intravitreal aflibercept in treatment-resistant neovascular age-related macular degeneration led to significant reduction in PED and SRF volume, central subfield thickness, and best-corrected visual acuity preserved, over 12 months. However, solid-type PED showed less improvement than hollow- or mixed-type PED.

Long-Term Outcomes of Full-Fluence and Half-Fluence Photodynamic Therapy for Chronic Central Serous Chorioretinopathy.

PURPOSE: To evaluate the efficacy and safety of full-fluence photodynamic therapy (PDT) and half-fluence PDT in chronic central serous chorioretinopathy (CSC). PROCEDURES: A retrospective review of CSC patients treated with full-fluence or half-fluence PDT for 12 months was performed. Best-corrected visual acuity (BCVA), central macular thickness (CMT), neural retinal thickness, subfoveal choroidal thickness (SFCT), resolution of subretinal fluid (SRF), and incidence of retinal pigment epithelium (RPE) atrophy at 12, 24, and 36 months were assessed. RESULTS: Thirty-seven and 30 eyes received full-fluence and half-fluence PDT, respectively. The BCVA and CMT improved significantly in both the full-fluence and half-fluence groups at 36 months, without a significant difference between the groups. Both groups showed significant reductions in SFCT with full-fluence (416.8-316.8 µm) being better overall than half-fluence (409.7-349.1 µm, p = 0.002). All patients achieved complete resolution without recurrence after one PDT treatment per eye. A few cases of RPE atrophy occurred, which could be correlated to PDT in both groups during the follow-up. CONCLUSION: Both treatments were effective and safe in chronic CSC, with significant improvements in anatomic and visual parameters, without recurrence of SRF.

Changes in aqueous concentrations of various cytokines after intravitreal bevacizumab and subtenon triamcinolone injection for diabetic macular edema.

PURPOSE: The purpose of this study was to compare the changes in the aqueous cytokine levels after intravitreal bevacizumab with those after combined intravitreal bevacizumab and subtenon triamcinolone injection in diabetic macular edema (DME). METHODS: This study examined 24 eyes of 23 patients with DME. Each patient with DME received randomly either an intravitreal injection of bevacizumab (IVBe) or IVBe with a subtenon triamcinolone injection (IVBe + STTA). Best corrected visual acuity and foveal thickness were evaluated and aqueous samples were obtained before and 4 weeks after the injection. The aqueous concentrations of interleukin (IL)-6, IL-8, interferon-induced protein (IP)-10, monocyte chemotactic protein (MCP)-1, platelet-derived growth factor (PDGF)-AA, and vascular endothelial growth factor (VEGF) were measured using a multiplex bead assay. RESULTS: After the injection, the foveal thickness decreased more in the IVBe + STTA group than in the IVBe group (P = 0.042). The MCP-1, PDGF-AA, and VEGF levels decreased significantly in the IVBe + STTA group (p = 0.013, p = 0.004 and p = 0.018 respectively), but only the VEGF level decreased in the IVBe group (p = 0.001). IL-8 was significantly increased in the IVBe + STTA group (p = 0.003) but the changes in the VEGF levels were smaller than in the IVBe group (p = 0.025). CONCLUSION: Intravitreal bevacizumab and subtenon triamcinolone injection reduces the VEGF, MCP-1 and PDGF-AA levels and increases the IL-8 level in the plural cytokine profiles of patients with DME, which might explain the limited therapeutic effect of combination therapy.

CORRELATION BETWEEN PREOPERATIVE EN FACE OPTICAL COHERENCE TOMOGRAPHY OF PHOTORECEPTOR LAYER AND VISUAL PROGNOSIS AFTER MACULAR HOLE SURGERY.

PURPOSE: To investigate the correlation between preoperative en face spectral domain optical coherence tomography findings of the photoreceptor layer with restoration of foveal microstructure and visual acuity in repaired macular holes. METHODS: Medical records of 106 patients with surgically closed macular holes were retrospectively reviewed. Preoperative OCT slabs of the external limiting membrane (ELM) and ellipsoid zone (EZ) were generated using embedded tools. All patients were classified into two groups according to the presence of preoperative retinal pigment epithelium protrusion seen as hyperreflective spots in EZ slab. Visual acuity, homogenous reflectivity, and glial proliferation in the ELM and EZ slabs were followed for 12 months. RESULTS: Baseline hyperreflective spots in the EZ slab was observed in 51 (48.1%) eyes. Postoperative homogenous reflectivity and glial proliferation were related to the presence of baseline hyperreflective spots. Vision improvement was significantly greater in the absence of hyperreflective spots group from 9 months after the operation. In logistic regression analysis, the area of hyperreflective spots was significantly associated with foveal homogenous reflectivity at 12 months (P = 0.004). CONCLUSION: Preoperative hyperreflective spots in en face EZ slab might be indicative of functional and anatomical restoration after macular hole surgery.

Substance P prevents development of proliferative vitreoretinopathy in mice by modulating TNF-α.

Purpose: Proliferative vitreoretinopathy (PVR) is an inflammatory fibrotic disease resulting from the inflammatory milieu after retinal detachment, which can prevent retinal healing. This study aimed to elucidate the effect of substance P (SP) on retinal degeneration caused by retinal detachment in vivo and to examine the role of SP in the tumor necrosis factor-alpha (TNF-α)-induced epithelial-mesenchymal transition (EMT) of human RPE cells in vitro. Methods: PVR-like retinal damage was induced by intravitreally injecting dispase into mice, and SP was systemically injected twice a week for 3 weeks. Histological analysis and cytokine profile with enzyme-linked immunosorbent assay (ELISA) were performed. The direct effect of SP on induction of EMT in vitro was studied by adding SP to TNF-α-treated ARPE-19 cells and then evaluating the change in the characteristics of the epithelial and mesenchymal cells. Results: Dispase injection led to a PVR-like retinal condition, demonstrating an inflammatory response with disruption of RPE interaction within 1 week and severe destruction with enfolding within 3 weeks after the dispase injection. The inflammatory environment promoted apoptosis and migration of fibroblast-like cells in the retinal layer, which can cause fibrotic disease, such as PVR. However, SP treatment suppressed early inflammatory responses by reducing TNF-α and elevating interleukin-10 (IL-10), with cell death and the appearance of fibroblastic cells inhibited and the progression of retinal degeneration obviously delayed. Moreover, SP ameliorated TNF-α-induced EMT of the RPE and directly prevented fibrotic change in the RPE. Conclusions: This study revealed that SP can block apoptosis and EMT due to retinal inflammation and inhibit the development of PVR. This effect most likely occurred by modulating the secretion and action of TNF-α..

AGE-RELATED CLINICAL OUTCOME AFTER MACULAR HOLE SURGERY.

PURPOSE: To evaluate functional and anatomical retinal recovery according to patient age using spectral domain optical coherence tomography in eyes with surgically closed macular holes. METHODS: We retrospectively studied 83 eyes with anatomically closed idiopathic macular holes after surgery confirmed by spectral domain optical coherence tomography. Patients were divided into four subgroups based on age (Group 1: ≤ 60, Group 2: 61-65, Group 3: 66-70, Group 4: > 70). Best-corrected visual acuity and reconstruction of the external limiting membrane and ellipsoid zone after surgery were documented for 12 months. RESULTS: Mean patient age was 64.5 ± 9.8 years (range 44-81). Mean visual improvement in logMAR units (ETDRS letter score) at 12 months was worse in older age subgroups (Group 1: 0.4 ± 0.3 [20], Group 2: 0.4 ± 0.3 [20], Group 3: 0.2 ± 0.3 [10], Group 4: 0.1 ± 0.3 [5], P = 0.001). When age was more than 65 years, total number of eyes with restored retinal microstructure after surgery was lower (22 eyes, 53.7%; 32 eyes, 76.2%; P = 0.018) and time (months) to structural recovery was longer (10.2, 7.1, P < 0.001) than age under 65 years. Visual improvement corresponded to recovery of the outer retinal layers. In multivariate analysis, patients of older age (odds ratio, 0.91; 95% CI, 0.89-0.93) had less visual improvement at month 12. CONCLUSION: Poor visual outcomes and delayed microstructural recovery occurred in older subjects after anatomically closed macular hole surgery. Older age may be indicative of poor clinical outcome in repaired macular holes.

Substance P promotes the recovery of oxidative stress-damaged retinal pigmented epithelial cells by modulating Akt/GSK-3ß signaling.

PURPOSE: Senescence of the retina causes an accumulation of reactive oxygen species (ROS). Oxidative stress associated with ROS can damage RPE cells, leading to neovascularization and severe ocular disorders, including age-related macular degeneration (AMD). Thus, the early treatment of the damage caused by oxidative stress is critical for preventing the development of ocular diseases such as AMD. In this study, we examined the role of substance P (SP) in the recovery of RPE cells damaged by oxidative stress. METHODS: To induce oxidative stress, RPE cells were treated with H2O2 at various doses. Recovery from oxidative stress was studied following treatment with SP by analyzing cell viability, cell proliferation, cell apoptosis, and Akt/glycogen synthase kinase (GSK)-3ß activation in RPE cells in vitro. RESULTS: H2O2 treatment reduced cellular viability in a dose-dependent manner. SP inhibited the reduction of cell viability due to H2O2 and caused increased cell proliferation and decreased cell apoptosis. Cell survival under oxidative stress requires the activation of Akt signaling that enables cells to resist oxidative stress-induced damage. SP treatment activated Akt/GSK-3ß signaling in RPE cells, which were damaged due to oxidative stress, and the inhibition of Akt signaling in SP-treated RPE cells prevented SP-induced recovery. Pretreatment with the neurokinin 1 receptor (NK1R) antagonist reduced the recovery effect of SP on damaged RPE cells. CONCLUSIONS: SP can protect RPE cells from oxidant-induced cell death by activating Akt/GSK-3ß signaling via NK1R. This study suggests the possibility of SP as a treatment for oxidative stress-related diseases.

Morphologic changes in the retina after selective retina therapy.

PURPOSE: To investigate structural changes in the retina by histologic evaluation and in vivo spectral domain optical coherence tomography (SD-OCT) following selective retina therapy (SRT) controlled by optical feedback techniques (OFT). METHODS: SRT was applied to 12 eyes of Dutch Belted rabbits. Retinal changes were assessed based on fundus photography, fluorescein angiography (FAG), SD-OCT, light microscopy, transmission electron microscopy (TEM), and scanning electron microscopy (SEM) at each of the following time points: 1 h, and 1, 3, 7, 14 and 28 days after SRT. BrdU (5'-bromo-2'-deoxy-uridine) incorporation assay was also conducted to evaluate potential proliferation of RPE cells. RESULTS: SRT lesions at1 h after SRT were ophthalmoscopically invisible. FAG showed leakage in areas corresponding to SRT lesions, and hyperfluorescence disappeared after 7 days. SD-OCT showed that decreased reflectivity corresponding to RPE damage was restored to normal over time in SRT lesions. Histologic analysis revealed that the damage in SRT lesions was primarily limited to the retinal pigment epithelium (RPE) and the outer segments of the photoreceptors. SEM and TEM showed RPE cell migration by day 3 after SRT, and restoration of the RPE monolayer with microvilli by 1 week after SRT. At 14 and 28 days, ultrastructures of the RPE, including the microvilli and tight junctions, were completely restored. The outer segments of the photoreceptors also recovered without sequelae. Interdigitation between the RPE and photoreceptors was observed. BrdU incorporation assay revealed proliferation of RPE on day 3 after SRT, and peak proliferation was observed on day 7 after SRT. CONCLUSION: Based on multimodal imaging and histologic assessment, our findings demonstrate that SRT with OFT could selectively target the RPE without damaging the neurosensory retina. Therefore, the use of SRT with OFT opens the door to the possibility of clinical trials of well-defined invisible and nondestructive retina therapy, especially for macular disease.