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Background/aimsEvaluation of the retinal nerve fibre layer (RNFL) is important for identifying glaucomatous damage. Ultrawide-field fundus photography (UWP) imaging is increasingly used in the ophthalmological field; however, it is unknown whether it can be used for detecting RNFL defects (RNFLDs). We investigated whether RNFLD can be detected with UWP images and compared the clinical effectiveness of three types of images for detecting RNFLD: conventional red-free RNFL photography (RFP), non-mydriatic UWP and digitally converted green separation of non-mydriatic UWP (G-UWP).MethodsEyes with glaucoma or glaucoma suspect and normal control eyes meeting the eligibility criteria were consecutively enrolled from September 2019 to April 2020. Their conventional RFP, non-mydriatic UWP and G-UWP images were assessed for detecting RNFLD to evaluate the sensitivity and specificity for detecting RNFLD.ResultsThree image sets of 196 participants (84 normal control, 25 glaucoma suspect and 87 glaucoma) were obtained. The sensitivity of G-UWP (94.6%; 95% CI 88.7 to 98.0) and RFP (92.9%; 95% CI 86.4 to 96.9) was higher than that of UWP (82.1%; 95% CI 73.8 to 88.7; pConclusionNon-mydriatic UWP images can be used to detect RNFLD. Non-mydriatic G-UWP showed comparable sensitivity but lower specificity to conventional RFP. Non-mydriatic G-UWP could be used as a convenient and useful diagnostic tool for screening glaucoma in clinical settings.

Kyuhwan Jang,1 Jayoung Ahn,1 Joonhong Sohn,1 Daniel Duck-Jin Hwang1,2 1Department of Ophthalmology, HanGil Eye Hospital, Incheon, Korea; 2Department of Ophthalmology, Catholic Kwandong University College of Medicine, Incheon, KoreaCorrespondence: Daniel Duck-Jin HwangDepartment of Ophthalmology, HanGil Eye Hospital, #35 Bupyeong-Daero, Bupyeong-Gu, Incheon 21388, KoreaTel +82-32-503-3322Fax +82-32-504-3322Email daniel.dj.hwang@gmail.comPurpose: To evaluate the short-term ophthalmic side effects of bilateral same-day intravitreal anti-vascular endothelial growth factor (VEGF) injections.Patients and Methods: We retrospectively analyzed patients who received intravitreal bevacizumab, ranibizumab, and aflibercept injections in both eyes on the same day between January 2014 and June 2019. The patients were followed up for 1 day, 1 week, and 1 month after the injections.Results: A total of 323 patients (646 eyes) received 1418 bilateral same-day intravitreal anti-VEGF injections. The patients’ mean age was 62.47 ± 13.97 years. The most common cause of bilateral injection was age-related macular degeneration (54.80%), followed by complications due to diabetic retinopathy (35.33%), retinal vein occlusion (2.40%), and central serious chorioretinopathy (1.27%). There were 22 cases of subconjunctival hemorrhage, 17 cases of temporary elevation of intraocular pressure, and no case of endophthalmitis. Twenty-one patients showed acute intraocular inflammation after the bilateral injection. All patients showed complete improvement within 2 weeks after the injection.Conclusion: Bilateral same-day intravitreal anti-VEGF injection is a well-tolerated procedure on short-term follow-up. It is one of the more convenient approaches for both the patient and ophthalmologist.Keywords: anti-vascular endothelial growth factor, bilateral intravitreal injection, bevacizumab, aflibercept, ranibizumab, safety

This cross-sectional study aimed to build a deep learning model for detecting neovascular age-related macular degeneration (AMD) and to distinguish retinal angiomatous proliferation (RAP) from polypoidal choroidal vasculopathy (PCV) using a convolutional neural network (CNN). Patients from a single tertiary center were enrolled from January 2014 to January 2020. Spectral-domain optical coherence tomography (SD-OCT) images of patients with RAP or PCV and a control group were analyzed with a deep CNN. Sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUROC) were used to evaluate the model’s ability to distinguish RAP from PCV. The performances of the new model, the VGG-16, Resnet-50, Inception, and eight ophthalmologists were compared. A total of 3951 SD-OCT images from 314 participants (229 AMD, 85 normal controls) were analyzed. In distinguishing the PCV and RAP cases, the proposed model showed an accuracy, sensitivity, and specificity of 89.1%, 89.4%, and 88.8%, respectively, with an AUROC of 95.3% (95% CI 0.727–0.852). The proposed model showed better diagnostic performance than VGG-16, Resnet-50, and Inception-V3 and comparable performance with the eight ophthalmologists. The novel model performed well when distinguishing between PCV and RAP. Thus, automated deep learning systems may support ophthalmologists in distinguishing RAP from PCV.

This study aimed to compare the surgical outcomes of pars plana vitrectomy (PPV) with and without air tamponade in patients with idiopathic epiretinal membrane (iERM). We prospectively enrolled 145 patients with iERM who underwent a 25-gauge transconjunctival sutureless PPV. Patients were assigned to either the air tamponade (air) group (79 eyes) or balanced salt solution (BSS; no tamponade) group (66 eyes). The central macular thickness (CMT), peripapillary retinal nerve fiber layer (pRNFL) thickness, and best-corrected visual acuity (BCVA) were compared for two years. At baseline, there were no significant differences between the two groups. CMT and BCVA were not significantly different between the groups for 2 years. However, the air group had a significantly lower thickness in the superior temporal pRNFL sector at 1 month (p = 0.01) and in the inferior temporal and superior temporal pRNFL sectors at 3 months (p = 0.02 for both). There were no significant differences between both groups in all the pRNFL sectors from 6 months to 2 years. The outcomes of PPV with air tamponade and that with no tamponade appear to be equivalent. This shows that air tamponade may not be an imperative procedure for iERM surgery and has no additional benefit.

The purpose is to evaluate the effects of multiple intravitreal ranibizumab (IVR) and aflibercept (IVA) injections on peripapillary retinal nerve fiber layer (RNFL) thickness in patients with exudative age-related macular degeneration (AMD). This retrospective, observational, consecutive case series study enrolled patients newly diagnosed with monocular exudative AMD from January 2014 to October 2019 who were administered IVR or IVA injections. Normal fellow eyes were included as controls. Medical records and spectral domain optical coherence tomography results were reviewed at baseline and at 3, 6, and 12 months after injection. No statistically significant differences in peripapillary RNFL thickness and intraocular pressure were observed between the treated and fellow eyes in the two groups. The global RNFL thicknesses for the treated eyes decreased significantly after 12 months compared with baseline, but no significant difference was observed in any of the six examined sectors (temporal, superior temporal, superior nasal, nasal, inferior nasal, and inferior temporal). At 12 months, the central macular thickness of the treated eyes decreased significantly. Multiple IVR and IVA injections are apparently safe considering peripapillary RNFL damage in patients with exudative AMD. The decreased RNFL thickness of the global sector was presumably due to anatomical improvement of macular lesions.

Central serous chorioretinopathy (CSC) is a common condition characterized by serous detachment of the neurosensory retina at the posterior pole. We built a deep learning system model to diagnose CSC, and distinguish chronic from acute CSC using spectral domain optical coherence tomography (SD-OCT) images. Data from SD-OCT images of patients with CSC and a control group were analyzed with a convolutional neural network. Sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUROC) were used to evaluate the model. For CSC diagnosis, our model showed an accuracy, sensitivity, and specificity of 93.8%, 90.0%, and 99.1%, respectively; AUROC was 98.9% (95% CI, 0.983–0.995); and its diagnostic performance was comparable with VGG-16, Resnet-50, and the diagnoses of five different ophthalmologists. For distinguishing chronic from acute cases, the accuracy, sensitivity, and specificity were 97.6%, 100.0%, and 92.6%, respectively; AUROC was 99.4% (95% CI, 0.985–1.000); performance was better than VGG-16 and Resnet-50, and was as good as the ophthalmologists. Our model performed well when diagnosing CSC and yielded highly accurate results when distinguishing between acute and chronic cases. Thus, automated deep learning system algorithms could play a role independent of human experts in the diagnosis of CSC.

PURPOSE To analyze the correlation between preoperative measurements of macular microstructures and aniseikonia after epiretinal membrane removal. METHODS This retrospective study included 32 eyes of 32 patients who underwent epiretinal membrane surgery and were followed up for 12 months. Spectral-domain optical coherence tomography was used to measure the thicknesses of the ganglion cell layer-inner plexiform layer, inner nuclear layer (INL), and outer retinal layer in macular microstructures. The new aniseikonia test was used to measure vertical and horizontal aniseikonia scores. RESULTS There was a significant decrease in central macular thickness and ganglion cell layer-inner plexiform layer thickness at 6 and 12 months postoperatively (all P < 0.001). Vertical aniseikonia scores, horizontal aniseikonia scores, and INL and outer retinal layer thicknesses did not show significant changes. Vertical aniseikonia scores and horizontal aniseikonia scores were significantly associated with INL thicknesses of each meridian at each follow-up time point (all P < 0.05). Preoperative vertical and horizontal INL thicknesses were correlated with vertical aniseikonia scores and horizontal aniseikonia scores at 12 months postoperatively (P = 0.014 and P = 0.002, respectively). CONCLUSION Aniseikonia values did not change after epiretinal membrane removal and were associated with INL thickness before and after surgery. Thus, preoperative INL thickness could be used as a predictor of surgical prognosis in epiretinal membrane patients.

Purpose To discuss the unique morphology and origin of epiretinal proliferation associated with macular hole (EPMH) occasionally observed in full-thickness macular hole (FT-MH) or lamellar hole (LH) and to introduce the perifoveal crown phenomenon encountered when removing this unusual proliferative tissue. Methods Sixteen patients showing EPMH in spectral domain-optical coherence tomography were selected from 212 patients diagnosed with MH, LH, FT-MH, impending MH, macular pseudohole, or epiretinal membrane between January 2013 and December 2014. Of the 212 patients included for clinical analysis, 33, 23, 11, 7, and 190 exhibited LH, FT-MH, impending MH, macular pseudohole, and epiretinal membrane, respectively. We reviewed visual acuity, macular morphology, and clinical course. Surgical specimens were analyzed histologically. Results EPMH presented as an amorphous proliferation starting from the defective inner/outer segment (IS/OS) junction covering the inner macula surface. Among the 16 patients with EPMH, 11 underwent vitrectomy, and all exhibited the intraoperative perifoveal crown phenomenon. EPMH tissue was sampled in three patients, one of whom had more tissue removed than intended and showed delayed recovery in visual acuity. Despite hole closure, IS/OS junction integrity was not successfully restored in four of 11 patients. Five patients were followed-up without surgical intervention. Visual acuity slightly decreased in three patients and did not change in one patient, while the remaining patient was lost during follow-up. Among the three perifoveal crown tissues obtained, two were successfully analyzed histologically. Neither tissue showed positivity to synaptophysin or S-100 protein, but one showed positivity to cytokeratin protein immunohistochemical staining. Conclusions EPMH exhibited a distinct but common configuration in spectral domain-optical coherence tomography. An epithelial proliferation origin is plausible based on its configuration and histological analysis. Perifoveal crown phenomenon was observed when removing EPMH during vitrectomy.

PURPOSE To assess optical quality and intraocular scattering using the Optical Quality Analysis System (OQAS) in central serous chorioretinopathy (CSC) and to determine the effects of retinal changes on optical quality. METHODS This was a prospective, case-control study. Participants were 29 patients with diagnosis of CSC. The control group consisted of the patients' unaffected eyes. Initial logMAR visual acuity, central macular thickness (by spectral domain optical coherence tomography), and optical quality parameters including modulation transfer function (MTF) cutoff frequency, Strehl (2-dimensional) ratio, and OQAS values at 100%, 20%, and 9% contrast levels were investigated. Objective scattering index (OSI) at 4.0-mm pupil size was assessed in both eyes by using the OQAS. After 3 months of treatment, which included observation and focal laser or injections of antivascular endothelial growth factor, every CSC-affected eye was followed. Main outcome measures were differences between clinical parameters of the CSC-affected eye and those of the control eye and changes in those parameters according to the clinical course of CSC over 3 months. RESULTS In CSC-affected eyes, the MTF cutoff was significantly reduced (P = 0.01), and OSI was significantly increased (P = 0.03). As macular thickness decreased, OSI decreased but did not become normalized compared to the control eye, nor was it statistically significantly correlated with central macular thickness change. CONCLUSIONS Retinal change affected optical quality and intraocular scatter. Therefore, when the severity of a cataract is assessed using the OQAS, retinal status should be considered when interpreting OQAS values.

Purpose To determine the origin of epiretinal proliferation (EP), a condition that is occasionally observed in lamellar hole and macular hole cases, and EP outcomes after vitrectomy. Methods This is a retrospective observational case review of 17 eyes with EP that underwent vitrectomy, EP dissection, and internal limiting membrane peeling between January 2013 and December 2016. Surgical specimens of EP tissue were successfully obtained from 5 cases and they were analyzed after immunohistochemical staining. Postoperative outcomes, including best-corrected visual acuity (BCVA) and macular configuration in spectral domain-optical coherence tomography, were reviewed. Results Mean BCVA improved from 0.54 ± 0.36 logarithms of the minimum angle of resolution preoperatively to 0.32 ± 0.38 logarithms of the minimum angle of resolution postoperatively (p = 0.002). BCVA improved in 13 eyes and remained unchanged in four eyes. No cases experienced vision decline after surgery. All 17 patients' lamellar hole or macular hole were successfully closed. Despite hole closure, ellipsoid zone defects were not corrected in 11 of the 17 patients. In immunohistochemical analyses, anti-glial fibrillary acidic protein and pan-keratin (AE1/AE3) were positive, but synaptophysin, anti-α-smooth muscle actin, and anti-CD68 were negative. Conclusions The epiretinal proliferative membrane seems to originate from Muller cells, not from the vitreous. It is unclear whether retinal pigment epithelia also contribute to EP formation. Gentle handling and preservation of the epiretinal proliferative tissue is crucial for successful surgical outcomes.

Purpose To analyze the morphologic evolution of idiopathic lamellar macular holes (LMHs) as determined by spectral domain optical coherence tomography, and evaluate the utility of retinal function assessments through multifocal electroretinography for predicting the likelihood of morphologic deterioration in LMHs. Methods Twenty-eight eyes of 28 patients with LMHs were examined by spectral domain optical coherence tomography at the initial visit and after 12 months. Lamellar macular holes were subdivided into morphologic deterioration (DET) and morphologic maintenance (MAI) groups based on the change in central retinal thickness during the follow-up period. Patients with LMHs were also examined by multifocal electroretinography at the initial visit. Multifocal electroretinography amplitudes were compared between DET and MAI groups, and discriminant function was calculated to predict morphologic deterioration in LMH eyes. Results During the follow-up period, morphologic deterioration was found in 8 (28.6%) of LMH cases. On multifocal electroretinography, amplitudes in the central ring (R1) and first paracentral ring (R2) were significantly lower in the DET than in the MAI group. Discriminant analysis performed on these two variables yielded a discriminant function with 75% of cases classified correctly. Conclusion Multifocal electroretinography is a useful tool for predicting morphologic deterioration of LMHs. Lower multifocal electroretinography amplitudes in R1 and R2 predict an increased risk of subsequent deterioration.

PURPOSE The purpose of this study was to identify the relationship between aniseikonia scores in the vertical and horizontal meridians and the foveal microstructure on vertical and horizontal spectral-domain optical coherence tomography (SD-OCT) in patients with idiopathic epiretinal membrane (ERM). METHODS All patients (n = 65) with unilateral ERM were examined, and the aniseikonia scores in the vertical (VAS) and horizontal (HAS) meridians were determined using the New Aniseikonia Test. Vertical and horizontal images passing through the fovea were obtained by axial SD-OCT in both eyes. The thicknesses of the ganglion cell layer + inner plexiform layer, inner nuclear layer (INL), and outer retinal layer were measured on the SD-OCT images, and color histograms were analyzed using Photoshop software. RESULTS Of the 65 ERM patients, 81.5% (53 patients) had macropsia. The VAS and HAS were equal in 52.8% (28 patients). Multiple regression analysis revealed significant correlations between the VAS and vertical INL thickness (R = 0.388, P = 0.001) and between the HAS and horizontal INL thickness (R = 0.349, P = 0.001). The difference between VAS and HAS was proportional to the ratio of the vertical INL thickness to horizontal INL thicknesses (R = 0.370, P < 0.001). CONCLUSIONS Eyes with ERM mostly presented macropsia. The aniseikonia scores in the vertical and horizontal meridians correlate well with INL thickness on the vertical and horizontal directions of SD-OCT images, respectively. Aniseikonia induced by ERM may be related to the INL thickening detected with SD-OCT.

Steroidal anti-inflammatory drugs induce proteins that inhibit phospholipase A(2) (PLA(2)), including uteroglobin and lipocortin-1 (annexin I). Uteroglobin and lipocortin-1 retain several conserved sequences. Based on these sequences, several nonapeptides (antiflammins) were synthesized. These nonapeptides were shown to have anti-inflammatory effects in vitro and in vivo, possibly by inhibiting PLA(2). Subsequent research showed that PLA(2) is activated by transglutaminase 2 (TGase 2). We hypothesize here that TGase 2 inhibitors may increase the anti-inflammatory efficacy of inhibiting PLA(2) activity. To test this theory, we constructed recombinant peptides containing sequences from pro-elafin (for inhibition of TGase 2), and from lipocortin-1, lipocortin-5, and uteroglobin (for inhibition of PLA(2)). The recombinant peptides, which had dual inhibitory effects on purified TGase 2 and PLA(2), reversed the inflammation of allergic conjunctivitis to ragweed in a guinea pig model. The present work suggests that novel recombinant peptides may be safe and effective agents for the treatment of various inflammatory diseases.

Purpose To develop a novel, simplified method for correcting the ischemic index of nonperfused areas in diabetic retinopathy (DR). Methods We performed a retrospective review of 103 eyes with naive DR that underwent ultra-widefield angiography (UWFA) over a year. UWFAs were graded according to the quantity of retinal non-perfusion, and uncorrected ischemic index (UII) and corrected ischemic index (CII) were calculated using a simplified, novel method. Results The average differences between UII and CII in the non-proliferative DR group and the proliferative DR group were 0.7 ± 0.9% in the 50% CII group, respectively. A CII >25% was critical for determining DR progression (p < 0.001). Conclusions Distortion created by UWFA needs to be corrected because the difference between UII and CII in DR increases with the ischemic index.

Objectives: To investigate patients with Proliferative Diabetic Retinopathy (PDR) using ultra-wide field fluorescein angiography (UWFA) images and to compare the detection rate of PDR progression using conventional seven standard field angiography (7SF) images. Methods: One hundred and one eyes of 67 patients with PDR who underwent fluorescein angiography using the Optos Optomap Panoramic 200A imaging system were included. Three hundred three images of 101 eyes at different time points (initial, Post-Panretinal Photocoagulation [PRP], and follow-up) were evaluated. In comparing 101 follow-up with 101 post-PRP images, we found newly developed Neovascularization (NNV) and newly developed non-perfusion (NNP) areas, which were then analyzed using two different methodologies: UWFA and 7SF. NNVs were counted while NNP area was measured in pixels using ImageJ software. Results: UWFA detected 21 eyes with NNV, which was approximately twice the number of eyes detected using 7SF (11 eyes). Ten eyes presented with NNV outside the 7SF area with apparently clean 7SF without NNV. UWFA detected 25 eyes with NNP areas, which was more than the six eyes detected using 7SF (19 eyes). Six eyes presented with NNP areas outside the 7SF, which were apparently fully perfused by 7SF. In addition, UWFA detected 2.59 times more NNP area than that by 7SF. Conclusion: Compared with conventional 7SF imaging, UWFA shows significantly improved retinal visualization and improves progression detection rates in patients with PDR.

Purpose: To determine if short term effects of intravitreal anti-vascular endothelial growth factor or steroid injection are correlated with fluid turbidity, as detected by spectral domain optical coherence tomography (SD-OCT) in diabetic macular edema (DME) patients. Methods: A total of 583 medical records were reviewed and 104 cases were enrolled. Sixty eyes received a single intravitreal bevacizumab injection (IVB) on the first attack of DME and 44 eyes received triamcinolone acetonide treatment (IVTA). Intraretinal fluid turbidity in DME patients was estimated with initialintravitreal SDOCT and analyzed with color histograms from a Photoshop program. Central macular thickness and visual acuity using a logarithm from the minimum angle of resolution chart, were assessed at the initial period and 2 months after injections. Results: Visual acuity and central macular thickness improved after injections in both groups. In the IVB group, visual acuity and central macular thickness changed less as the intraretinal fluid became more turbid. In the IVTA group, visual acuity underwent less change while central macular thickness had a greater reduction (r = -0.675, p = 0.001) as the intraretinal fluid was more turbid. Conclusions: IVB and IVTA injections were effective in reducing central macular thickness and improving visual acuity in DME patients. Further, fluid turbidity, which was detected by SD-OCT may be one of the indexes that highlight the influence of the steroid-dependent pathogenetic mechanism.

To evaluate the effect of chlorogenic acid (CGA), a polyphenol abundant in coffee, on retinal vascular leakage in the rat model of diabetic retinopathy, Sprague-Dawley rats were divided into four groups: controls, streptozotocin-induced diabetic rats, and diabetic rats treated with 10 and 20 mg/kg chlorogenic acid intraperitoneally daily for 14 days, respectively. Blood-retinal barrier (BRB) breakdown was evaluated using FITC-dextran. Vascular endothelial growth factor (VEGF) distribution and expression level was evaluated with immunohistochemistry and Western blot analysis. Expression of tight junction proteins, occludin and claudin-5, and zonula occludens protein, ZO-1 was also evaluated with immunohistochemistry and Western blot analysis. BRB breakdown and increased vascular leakage was found in diabetic rats, with increased VEGF expression and down-regulation of occludin, claudin-5, and ZO-1. CGA treatment effectively preserved the expression of occludin, and decreased VEGF levels, leading to less BRB breakdown and less vascular leakage. CGA may have a preventive role in BRB breakdown in diabetic retinopathy by preserving tight junction protein levels and low VEGF levels.

Branch retinal vein occlusion (BRVO) is the second most common major retinal vascular disease after diabetic retinopathy [1]. Epidemiologic studies found that the prevalence of BRVO ranged from 0.3% [2] to 1.6% [3], and major risk factors for the condition were increasing age, hypertension, and co-existing cardiovascular disease [2-6]. Macular edema is a major cause of visual acuity loss attributable to BRVO [7-9]. The Branch Vein Occlusion Study [7] found that grid photocoagulation was effective for treatment of macular edema. The Standard Care vs Corticosteroid for Retinal Vein Occlusion (SCORE) project showed that grid photocoagulation was the best option for standard care when used to treat macular edema secondary to BRVO [10]. In recent decades, several novel treatments for BRVO have been introduced in major studies such as the BRAVO [11] and GENOVA studies [12]. However, the effects of such treatments remain unclear [1,9,13]. Furthermore, the cited works did not mimic the true clinical situation in that intravitreal bevacizumab injections (IVBs) were consecutively administered over a 3-month period to form a loading dose, the treatment strategy to be adopted after initial treatment failure was not considered, and lastly, no study has compared intravitreal triamcinolone acetate, bevacizumab, and drug combination injections for the treatment of macular edema secondary to BRVO. In the present study, we reviewed the medical records of patients treated for visual loss caused by macular edema secondary to BRVO 1) to evaluate whether intravitreal triamcinolone acetate, bevacizumab, and a combination of triamcinolone and bevacizumab injections, with or without rescue laser therapy, improved visual acuity compared with standard care of the type administered in the SCORE study, and 2) to determine whether such treatment modalities reduced unfavorable outcomes in patients with macular edema caused by BRVO, compared with those of the SCORE study.

Purpose To evaluate the functional changes in various morphologic types of idiopathic epiretinal membrane (ERM) by multifocal electroretinography (mfERG) and spectral-domain optical coherence tomography (SD-OCT). Methods All patients (n = 71) with unilateral idiopathic ERM underwent complete ophthalmologic examination, including measurements of best-corrected visual acuity (BCVA), SD-OCT, and mfERG for both eyes. To classify idiopathic ERM by subtype, the morphologic characteristics of the foveal area on representative scanned images were assessed. The five subtypes by foveal SD-OCT morphology included fovea-attached ERM with outer retinal thickening and minimal inner retinal change (Group 1A), outer retinal inward projection and inner retinal thickening (Group 1B), and prominent thickening of inner retinal layer (Group 1C) and foveal sparing ERM with formation of macular pseudohole (Group 2A) and with schisislike, intraretinal splitting (Group 2B). Results On mfERG, P1 amplitude density in the central ring (R1) and inter-eye (affected eye/fellow eye) response ratio of P1 amplitude density in R1 differed significantly among five groups (P = 0.032 and P = 0.022, respectively). In Group 1 patients, central subfield thickness (CST) and inner retinal layer thickness (IRT) on SD-OCT were strongly correlated with BCVA and P1 amplitude density in R1. A receiver operating characteristic (ROC) curve analysis showed that IRT had high predictive accuracy in distinguishing Groups 1A and 1B (area under the ROC curve [AUROC] = 0.966) and Groups 1B and 1C (AUROC = 1.000). Conclusions Multifocal electroretinography can be used to investigate the pathophysiology of ERM and to evaluate the degree of functional demise in the fovea on SD-OCT.

Using a 193 nm excimer laser, we performed elliptical astigmatic and spherical corneal ablation on 168 eyes with compound myopic astigmatism and analyzed the three- and six-month postoperative results. Mean preoperative astigmatism was 1.51 +/- 0.81 diopters (D). Mean three- and six-month postoperative astigmatism was 0.70 +/- 0.58 D and 0.67 +/- 0.60 D, respectively. Six months after surgery, eyes with less than 1.00 D preoperative astigmatism improved 4.8%. The improvement was 53.5% and 59.1% for eyes with a preoperative astigmatism of 1.00 D to 2.00 D and above 3.00 D, respectively. Overall, astigmatism improved 55.6%. There was a wide distribution from overcorrection to undercorrection. Astigmatism six months after surgery was within 10 degrees of the preoperative axis in 46.1% of eyes.

Angiogenesis, the process by which new blood vessels are formed, is tightly regulated by a balance between positive and negative factors [1]. Pathologic angiogenesis in the eye is the major cause of blindness in such conditions as retinopathy of prematurity, age-related macular degeneration (AMD), and diabetic retinopathy. AMD is the leading cause of blindness in persons over the age of 55 years in developed countries [2]. Although the detailed disease mechanism is not sufficiently understood as of yet, choroidal neovascularization (CNV) leads to severe vision loss in patients with AMD. CNV invades the subretinal space through choroidal vessel proliferation following rupture of Bruch's membrane. Vascular endothelial growth factor (VEGF) has been shown to be a key mediator of angiogenesis and a vascular permeability-enhancing factor during the development of CNV [3]. Chlorogenic acid, the ester of caffeic acid with quinic acid, is one of the most abundant polyphenol compounds in the human diet. It is a major phenolic compound in coffee, is widespread in plants, and can be isolated from leaves and fruit [4]. This compound, long known as an antioxidant [5], has also been reported to have anti-inflammatory properties [6], anticarcinogenic activities [7,8], and protective effects on neuronal cells [9]. Furthermore, epidemiological studies have highlighted the association between the consumption of polyphenol-rich foods and beverages and the prevention of type 2 diabetes mellitus and cardiovascular disease [10-12]. In the study presented here, we investigated the anti-angiogenic effects of chlorogenic acid on laser-induced CNV in a rat model.

PURPOSE. To evaluate the effect of N-4-hydroxyphenyl retinamide (4-HPR) on experimental laser-induced choroidal neovascularization (CNV) and on the expression and secretion of relevant growth factors by cultured human retinal pigment epithelial (RPE) cells. METHODS. CNV was induced by laser photocoagulation in C57BL/6 mice. 4-HPR (0.2 or 1 mg) or vehicle, was injected intraperitoneally twice daily for 14 days. Plasma and tissue levels of 4-HPR were measured by HPLC. CNV was evaluated by fluorescein angiography, histology, and quantitative confocal analysis of isolectin B4 histochemistry on days 7 and 14. Induction of apoptosis and expression and secretion of growth factors was studied in 4-HPR-treated RPE cultures. RESULTS. Mice treated with 4-HPR exhibited time- and dose-dependent increases in plasma and tissue 4-HPR levels. CNV lesions showed increased volume with increased vascular leakage and contained fewer lesion-associated RPE in treated versus untreated mice. Treatment of nonpolarized RPE cultures with 4-HPR in the presence of serum resulted in RPE apoptosis; however, apoptosis was minimal in similarly treated highly polarized RPE. Treatment of RPE cells with 4-HPR resulted in the upregulation of VEGF-A and -C (P < 0.05) and Ang-1 (P < 0.01) mRNA and increased secretion of VEGF-A and -C (P < 0.05), whereas pigment epithelium-derived growth factor (PEDF) and thrombospondin (TSP)-1 mRNA expression and secretion were downregulated (P < 0.05). CONCLUSIONS. 4-HPR increases lesion size and leakage in laser-induced CNV and is associated with the upregulation of key proangiogenic factors and the downregulation of antiangiogenic factors. Consistent with the preferential loss of RPE in CNV lesions in vivo, 4-HPR induces apoptosis of nonpolarized RPE in the presence of serum.

To investigate the postnatal risk factors of retinopathy of prematurity (ROP), we analysed demographic and clinical data abstracted from the medical records of 425 premature babies who were examined for ROP between January 1994 and December 1998 at Asan Medical Centre, Seoul, Korea. ROP developed in 20.7% of the cases studied. A gestational age (GA) ofor = 28 weeks and birthweight (BW) ofor = 1000 g were the most significant risk factors. Ventilator care foror = 48 h, apnoea, and use of surfactant independently increased the incidence of ROP. Furthermore, frequent apnoeic attacks increased the progression of pre-threshold ROP to threshold ROP. Therefore, as well as GA and BW, apnoea, prolonged use of a ventilator, and surfactant therapy are significant independent risk factors for ROP. In addition, apnoea may not only increase the risk of developing ROP, but may also worsen pre-existing ROP.

PURPOSE To report clinical features of uveal metastatic tumors in Korean patients who have different cancer profiles than those of patients in Western countries. METHODS The authors performed a retrospective chart review on all patients with evaluated uveal metastases. RESULTS Fourteen patients were diagnosed. One eye involved the iris, and 14 eyes of 13 patients involved the choroid. The metastases came from a primary cancer of the breast in four (29%), the lung in four (29%), the stomach in two (14%), the esophagus in one (7%), the common bile duct in one (7%), the kidney in one (7%), and unknown in one (7%). Thirteen (93%) of 14 choroidal metastases were associated with subretinal fluid, and eight (57%) eyes had tumors that were posterior to the equator. At the time of diagnosis, all patients had a history of cancer, and 11 patients had a metastatic lesion elsewhere. Three patients were undergoing chemotherapy. All three cases from gastric or esophageal cancer had a thicker choroidal mass and massive exudative retinal detachment. CONCLUSIONS The authors' series of uveal metastases showed a higher incidence from gastrointestinal cancer in Korean patients. Choroidal tumors from gastric or esophageal cancer seemed to be larger with massive exudation.

PURPOSE To determine the role of pars plana vitrectomy (PPV) in the treatment of Klebsiella pneumoniae endogenous endophthalmitis. METHODS Records of seven consecutive patients (10 eyes) diagnosed with Klebsiella endogenous endophthalmitis were retrospectively reviewed. RESULTS Five patients (71%) had diabetes, and four (57%) had a liver abscess as the source. In most cases, the inflammation progressed within days and resulted in decreased vision worse than hand motions and a total vitreous abscess, despite systemic and intravitreal antibiotic injections. A PPV with subretinal abscess drainage and silicone oil tamponade was performed within 2 weeks. After 6 months, the retina remained attached in all eyes (100%), and vision was counting fingers or better in five eyes (50%). Two eyes recovered visual acuity between 20/63 and 20/125. CONCLUSIONS Physicians should be alerted to the development of endogenous endophthalmitis in patients with Klebsiella septicemia, especially in diabetics with a hepatobiliary abscess. Aggressive therapy, including early vitrectomy with antibiotic injection, may improve the final outcome in this otherwise devastating ocular condition.

Although zinc deficiency may contribute to age-related macular degeneration (ARMD), the pathogenic mechanism is as yet uncertain. In light of evidence that cellular zinc depletion induces apoptosis in cortical neurons and thymocytes, in the present study, we examined the possibility that the same phenomenon occurs also in retinal cells. Exposure of primary retinal cell cultures to 1-3 microM of a cell membrane-permeant zinc chelator TPEN for 24 h induced concentration-dependent death of neurons, photoreceptor cells, and astrocytes. Addition of zinc or copper reversed TPEN toxicity to all cell components, indicating the particular involvement of zinc chelation in cell death. Consistent with apoptosis, oligonucleosomal DNA fragmentation and chromatin condensation accompanied, and the protein synthesis inhibitor cycloheximide blocked the TPEN-induced retinal cell death. During TPEN-induced retinal cell apoptosis, cleavage/activation of procaspase-1, but little of procaspase-3, was observed. Consistent with this finding, a broad-spectrum caspase inhibitor (zVAD-fmk) was significantly more protective than a caspase-3-selective inhibitor (DEVD-fmk). The present study has demonstrated that depletion of intracellular zinc is sufficient to induce macromolecule synthesis- and caspase-dependent apoptosis of cultured retinal cells. In light of the possibility that zinc depletion may contribute to the pathogenesis of ARMD, the current culture model may be a useful tool for the investigation of the mechanism of zinc depletion-induced retinal cell death.

We studied a case of unusual retinopathy in a 35-year-old woman who presented with bilateral visual deterioration due to retinal pigmentary mottling and serous elevation in the posterior pole. Two years before, she had undergone hysterectomy and bilateral salphingo-oophorectomy for ovarian cancer. Her electroretinogram became subnormal, and her fluorescein angiogram exhibited multiple deep retinal pigment epithelial leakages and subretinal dye pooling in both eyes. Corticosteroid therapy failed to prevent visual loss. She was found to possess antibodies against retinal 45 kd protein. This led to a diagnosis of cancer-associated retinopathy with atypical protein profile. We report a rare variety of cancer-associated retinopathy in a patient with-ovarian cancer.

Purpose: Our goal was to investigate the effects of inhibition of transglutaminase 2 (TGase 2) on endotoxin-induced uveitis (EIU) Methods: EIU was induced in female Lewis rats by single footpad injections of 200 μ g of lipopolysaccharide (LPS). TGase 2 inhibitors were administered intraperitoneally 30 minutes before and at the time of LPS administration. Rats were sacrificed 24 hours after injection, and the effects of the TGase 2 inhibitors were evaluated by the number of intraocular inflammatory cells present on histologic sections and by measuring the TGase 2 activity and TGase products in the aqueous humor (AqH). TGase 2 substrates were also assayed in AqH from uveitis patients. Results: Clinical indications of EIU, the number of cells present on histologic sections, and TGase 2 activity in AqH increased in a time-dependent manner, peaking 24 hours after LPS injection. Inflammation in EIU was significantly reversed by treatment with TGase inhibitors. A 23-kDa cross-linked TGase substrate was identified in the AqH from EIU rats and uveitis patients. MALDI-TOF analysis showed that this substrate in uveitis patients was human Ig kappa chain C region. Conclusions: TGase 2 activity and its catalytic product were increased in the AqH of EIU rats. TGase 2 inhibition attenuated the degree of inflammation in EIU. Safe and stable TGase inhibitors may have great potential for the treatment of inflammatory uveitis.

Oxidative stress has been proposed as a major injury mechanism in the central nervous system including the retina. In this study, as an initial attempt to study the mechanism of oxidative injury in the retina, we developed a cell culture model by utilizing the iron exposure paradigm. Exposure of rat retinal cultures for 24 hours to 10-40 MicroM ferrous or ferric chloride induced a concentration-dependent death of retinal neurons but not of photoreceptors or astrocytes. An antioxidant, trolox effectively attenuated the iron-induced death of neurons and photoreceptors in a dose-dependent manner whereas neither glutamate receptor antagonists nor cycloheximide were protective. Of retinal interneurons, GABAergic neurons were more vulnerable to the iron toxicity than calbindin (+) horizontal neurons. These findings show that iron exposure induces anti-oxidant-sensitive neuronal injury in retinal culture, independent of the excitotoxic or the apoptotic mechanisms. Of retinal neurons, different cell types exhibit differential vulnerabilities to the iron-induced oxidative injury. This simplified culture model system may be useful in elucidating mechanisms of oxidative injury in the retina.