Effect of Anti-glaucoma Agents on Myopic Retinoschisis

Purpose@#To evaluate the effect of intraocular pressure (IOP)-lowering medications on myopic retinoschisis. @*Methods@#The medical records of 33 patients (36 eyes) with myopic retinoschisis associated with pathologic myopia were reviewed retrospectively. The patients were divided into two groups: the study group comprising patients undergoing treatment with anti-glaucoma medications for suspected glaucoma; the control group comprising patients who did not use any IOP lowering medications. The changes in retinoschisis in the two groups were compared using the Spectralis domain optical coherence tomography thickness map protocol. @*Results@#The study group included 18 eyes (17 patients), and the control group included 18 eyes (16 patients). There were no significant differences between the 6-month and 12-month improvement or aggravation rates of the two groups (p = 0.513 and 0.137, respectively). However, after 18 months, the aggravation rate of retinoschisis was significantly lower in the study group (p = 0.003). The improvement / aggravation rate was 58.33% / 16.67% in the study group and 0% / 57.14% in the control group. @*Conclusions@#The use of IOP-lowering medications for more than a year may be useful for the management of retinoschisis associated with pathologic myopia.

Effect of Anti-glaucoma Agents on Myopic Retinoschisis

Purpose@#To evaluate the effect of intraocular pressure (IOP)-lowering medications on myopic retinoschisis. @*Methods@#The medical records of 33 patients (36 eyes) with myopic retinoschisis associated with pathologic myopia were reviewed retrospectively. The patients were divided into two groups: the study group comprising patients undergoing treatment with anti-glaucoma medications for suspected glaucoma; the control group comprising patients who did not use any IOP lowering medications. The changes in retinoschisis in the two groups were compared using the Spectralis domain optical coherence tomography thickness map protocol. @*Results@#The study group included 18 eyes (17 patients), and the control group included 18 eyes (16 patients). There were no significant differences between the 6-month and 12-month improvement or aggravation rates of the two groups (p = 0.513 and 0.137, respectively). However, after 18 months, the aggravation rate of retinoschisis was significantly lower in the study group (p = 0.003). The improvement / aggravation rate was 58.33% / 16.67% in the study group and 0% / 57.14% in the control group. @*Conclusions@#The use of IOP-lowering medications for more than a year may be useful for the management of retinoschisis associated with pathologic myopia.

Epiretinal Proliferation Associated with Lamellar Hole or Macular Hole: Origin and Surgical Prognosis

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 Müller 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.

Epiretinal Proliferation Associated with Macular Hole and Intraoperative Perifoveal Crown Phenomenon

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.

Simplified Correction of Ischemic Index in Diabetic Retinopathy Evaluated by Ultra-widefield Fluorescein Angiography

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.

Simplified Correction of Ischemic Index in Diabetic Retinopathy Evaluated by Ultra-widefield Fluorescein Angiography

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.

Efficacy of Intravitreal Anti-vascular Endothelial Growth Factor or Steroid Injection in Diabetic Macular Edema According to Fluid Turbidity in Optical Coherence Tomography

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 SD-OCT 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.

Comparison of Injection of Intravitreal Drugs with Standard Care in Macular Edema Secondary to Branch Retinal Vein Occlusion

PURPOSE: To compare the long-term efficacy and safety of intravitreal triamcinolon with or without rescue laser therapy (intravitreal triamcinolone injection [IVTA] group), bevacizumab with or without rescue laser treatment (intravitreal bevacizumab injection [IVB] group), or a combination of both with or without rescue laser therapy (IVTA + IVB group), with standard care for patients with macular edema secondary to branch retinal vein occlusion (BRVO). METHODS: We reviewed the medical records of 151 patients treated with intravitreal injection with or without rescue laser for treatment of macular edema caused by BRVO, and who were followed up at 1, 3, 6, 12, and 24 months. During the observation period, rescue grid laser or repeated intravitreal injection with initial drug was performed if recurrence of macular edema was confirmed. Visual acuity, change in visual acuity, and intraocular pressure were compared in each phase. RESULTS: Totals of 16%, 5.6%, and 0% of participants in the three groups showed significant visual loss of more than three lines of the Snellen chart at last follow-up. The IVTA group was the least effective treatment modality, with statistical significance. The development rates of elevated intraocular pressure were similar among the groups. CONCLUSIONS: Although IVTA yielded effects similar to those of standard grid photocoagulation based on the Standard Care vs Corticosteroid for Retinal Vein Occlusion study, IVB or IVTA + IVB with or without rescue laser treatment resulted in improvement in visual acuity at 24 months after the start of treatment and was associated with few serious adverse side effects. Thus, these approaches could be useful for treating macular edema arising secondary to BRVO.

Comparison of Injection of Intravitreal Drugs with Standard Care in Macular Edema Secondary to Branch Retinal Vein Occlusion

PURPOSE: To compare the long-term efficacy and safety of intravitreal triamcinolon with or without rescue laser therapy (intravitreal triamcinolone injection [IVTA] group), bevacizumab with or without rescue laser treatment (intravitreal bevacizumab injection [IVB] group), or a combination of both with or without rescue laser therapy (IVTA + IVB group), with standard care for patients with macular edema secondary to branch retinal vein occlusion (BRVO). METHODS: We reviewed the medical records of 151 patients treated with intravitreal injection with or without rescue laser for treatment of macular edema caused by BRVO, and who were followed up at 1, 3, 6, 12, and 24 months. During the observation period, rescue grid laser or repeated intravitreal injection with initial drug was performed if recurrence of macular edema was confirmed. Visual acuity, change in visual acuity, and intraocular pressure were compared in each phase. RESULTS: Totals of 16%, 5.6%, and 0% of participants in the three groups showed significant visual loss of more than three lines of the Snellen chart at last follow-up. The IVTA group was the least effective treatment modality, with statistical significance. The development rates of elevated intraocular pressure were similar among the groups. CONCLUSIONS: Although IVTA yielded effects similar to those of standard grid photocoagulation based on the Standard Care vs Corticosteroid for Retinal Vein Occlusion study, IVB or IVTA + IVB with or without rescue laser treatment resulted in improvement in visual acuity at 24 months after the start of treatment and was associated with few serious adverse side effects. Thus, these approaches could be useful for treating macular edema arising secondary to BRVO.

Chlorogenic Acid Decreases Retinal Vascular Hyperpermeability in Diabetic Rat Model

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.

The Anti-angiogenic Effect of Chlorogenic Acid on Choroidal Neovascularization

PURPOSE: To evaluate the inhibitory effect of chlorogenic acid on laser-induced choroidal neovascularization (CNV) in a rat model. METHODS: Intraperitoneal injection of chlorogenic acid (10 mg/kg) was inititated one day prior to laser photocoagulation and continued for eight days. Eyes were removed 14 days after laser photocoagulation. Fluorescein angiography was employed at seven and 14 days to assess the CNV lesions, and histological examination was performed. Quantification of CNV size and leakage were performed both in histological sections and fluorescein angiography in order to compare the inhibitory effects of chlorogenic acid on CNV with the results of the control. RESULTS: Histological analysis showed no significant difference in CNV size between the treated and control groups. However, CNV leakage on fluorescein angiography had significantly decreased in the chlorogenic acid-treated group at 14 days after laser photocoagulation compared with that of the control group. In addition, CNV size on fluorescein angiography had significantly decreased in the treated group at seven and 14 days. CONCLUSIONS: These results suggest that chlorogenic acid has anti-angiogenic effects on CNV and may be useful as an inhibitor in the treatment or prevention of neovascular age-related macular degeneration.

A Novel Therapeutic Target in Inflammatory Uveitis: Transglutaminase 2 Inhibitor

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 microgram 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.

Outcome of Vitreoretinal Surgery and Penetrating Keratoplasty using Temporary Keratoprosthesis

PURPOSE: Using a temporary keratoprosthesis(TKP), earlier surgical treatment became amenable in eyes with coexisting vitreoretinal and corneal disease. We analysed our experience with this type of surgery. METHOD: Medical records of patients who had undergone pars plana vitrectomy(PPV) using Eckardt TKP from 1994 to 2000 were reviewed. Analysis was focused on preoperative conditions, surgical outcome and complications. RESULT: Of 34 eyes of consecutive 34 patients, 25(73.5%) showed trauma-related indications and 4 had IOFB. Retinal detachments were present in 24(70.6%) eyes, proliferative vitreoretinopathy in 8(23.5%) and vitreous hemorrhage in 10(29.4%) eyes. Penetrating keratoplasty(PKP) with donor corneas were performed in only 3 patients at the time of surgery and patient's excised corneas were sutured to 31 patients, 9 of whom underwent PKP later. After mean follow up period of 14 months, retinas remained attached in 27(79.4%) eyes and 3 eyes were phthisical. Visual acuity improved in 18(53%) eyes and worsened in 5 eyes. CONCLUSIONS: In cases with coexisting corneal and vitreoretinal pathology, PPV using TKP was effective for preserving vision and globe. Timing of grafting clear cornea might be delayed when donor cornea was not available.