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   Table of Contents - Current issue
Coverpage
October-December 2019
Volume 9 | Issue 4
Page Nos. 213-294

Online since Friday, December 13, 2019

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EDITORIAL  

The omnipresence of vascular endothelial growth factor in retinal diseases p. 213
Lihteh Wu
DOI:10.4103/tjo.tjo_73_19  
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REVIEW ARTICLES Top

Vascular endothelial growth factor inhibition and proliferative diabetic retinopathy, a changing treatment paradigm? p. 216
Lihteh Wu, Dhariana Acón, Andrés Wu, Max Wu
DOI:10.4103/tjo.tjo_67_19  
Prior to the development of panretinal photocoagulation (PRP) in the 1970s, proliferative diabetic retinopathy (PDR) was the most common cause of blindness in diabetic patients. The diabetic retinopathy study demonstrated that PRP could decrease severe visual loss from PDR by 50%. Since then and for the past four decades, PRP has been the treatment of choice for eyes with PDR. In the past decade, vascular endothelial growth factor (VEGF) inhibition has become the treatment of choice for diabetic macular edema (DME). When treated intensively with anti-VEGF drugs, about one-third of eyes with DME experience an improvement in their diabetic retinopathy severity scale. Randomized clinical trials comparing ranibizumab to PRP and aflibercept to PRP have shown that VEGF inhibitors cause regression of intraocular neovascularization but need to be given on a fairly regular basis. Despite these promising results, concerns about treatment adherence have surfaced. Patients with PDR that are treated solely with anti-VEGF drugs and somehow interrupt their treatment are at a high risk of developing irreversible blindness. Combination treatment of PRP plus an anti-VEGF drug may be the treatment of choice for PDR.
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Revisiting pars plana vitrectomy in the primary treatment of diabetic macular edema in the era of pharmacological treatment p. 224
Stephanie Flikier, Andres Wu, Lihteh Wu
DOI:10.4103/tjo.tjo_61_19  
Diabetic macular edema (DME) is the most common cause of moderate visual loss in diabetic patients. The current treatment of choice for center-involved DME is anti-vascular endothelial growth factor (VEGF) treatment. Most patients that undergo pharmacological inhibition with anti-VEGF agents need multiple monitoring visits that include optical coherence tomography imaging and multiple injections. Despite this intensive treatment, up to 60% of eyes will have persistent DME after six consecutive monthly injections of an anti-VEGF. Its sustainability over the long term has been questioned. Pars plana vitrectomy (PPV) by increasing the vitreous cavity oxygenation, relieving vitreomacular traction, and removing cytokines from the vitreous cavity may cause long-term resolution of DME without the aforementioned concerns in selected cases. Eyes with vitreomacular traction clearly benefit from PPV as the primary treatment. The role of PPV for eyes with DME without tractional elements is less clear and needs to be explored further.
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Corticosteroids for diabetic macular edema p. 233
Jorge Chawan-Saad, Max Wu, Andres Wu, Lihteh Wu
DOI:10.4103/tjo.tjo_68_19  
Diabetic macular edema (DME) is a chronic condition with a multifactorial pathogenesis. Vascular endothelial growth factor (VEGF) and several inflammatory mediators are upregulated in eyes with DME. VEGF inhibitors and corticosteroids have all been used successfully in the management of DME. Currently available corticosteroids include triamcinolone acetonide (TA), the dexamethasone (DEX) intravitreal implant, and the fluocinolone acetonide (FA) intravitreal implant. The response to treatment can vary substantially with each treatment modality. Some cases of DME are VEGF driven, and in others, inflammation plays a key role. Chronicity appears to favor corticosteroid treatment. There are no clear guidelines to guide switching from an anti-VEGF to a corticosteroid. Combination therapy of an anti-VEGF drug and a corticosteroid does not appear to provide additional benefit over monotherapy with either drug. The main advantage of corticosteroids over VEGF inhibitors is their longer duration of action. Vitrectomy does not affect the pharmacokinetics of the corticosteroid implants. Common adverse events of corticosteroids include cataract formation, cataract progression, and ocular hypertension. TA may cause a sterile endophthalmitis and pseudoendophthalmitis. Migration of the intravitreal DEX and FA implants into the anterior chamber can be problematic. Because of their less favorable safety profile, corticosteroids are generally used as a second-line treatment for DME. Advantages of using an intravitreal corticosteroid implant include the reduction of treatment burden and predictable pharmacokinetics even in vitrectomized eyes. Pseudophakic eyes, previously vitrectomized eyes and eyes with long-standing DME, particularly of patients who have difficulty in maintaining a monthly appointment, may benefit from primary treatment with a corticosteroid intravitreal implant.
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ORIGINAL ARTICLES Top

Genetic association with intravitreal ranibizumab response for neovascular age-related macular degeneration in Hispanic population p. 243
Francisco Jose Rodriguez, Hernan Andres Rios, María Camila Aguilar, Shirley Margarita Rosenstiehl, Nancy Gelvez, Greizy Lopez, Martha L Tamayo
DOI:10.4103/tjo.tjo_72_19  
BACKGROUND/PURPOSE: Age-related macular degeneration (AMD) is the leading cause of visual impairment in patients over 55 years. Currently, the most common therapies for neovascular AMD (nAMD) are intravitreal antiangiogenics. Studies suggest that genetic factors influence on antiangiogenics therapy outcomes. The purpose of this work was to establish the association between complement factor H (CFH) (Y402H), age-related maculopathy susceptibility 2 (ARMS2) (A69S), and high-temperature requirement factor A1 (HTRA1) (rs11200638) polymorphisms and the response to treatment with ranibizumab in patients with nAMD. METHODS: A cross-sectional study with 61 eyes with nAMD treated with ranibizumab was performed. Association between polymorphisms from CFH, ARMS2, and HTRA1 with the response to treatment was established. RESULTS: The mean age of patients was 76.6 (51–91) years. Only 37.7% of patients had a functional response and 26.2% had an anatomic response. TT polymorphism Y402H from CFH gene was associated with an increased likelihood of functional response to treatment. Otherwise, there was not a statistically significant association between anatomic and functional response to gene polymorphisms rs11200638 from HTRA1 and rs10490924 from ARMS 2. CONCLUSIONS: This study suggests that the response to intravitreal antiangiogenic therapy with ranibizumab was not associated to main polymorphisms from genes HTRA1 and ARMS2. However, it was found that the response to treatment differed according to CFH genotype, suggesting that further investigations are needed to establish if patients with the CC and TC genotype may need to be monitored more closely for disease recurrence than the TT genotype.
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Real-world outcomes of intravitreal antivascular endothelial growth factors for neovascular age-related macular degeneration in Taiwan: A 4-year longitudinal study p. 249
Benjamin Chi-Lan Yang, Terry Yu-Hung Chou, San-Ni Chen
DOI:10.4103/1027-8117.271504  
PURPOSE: The purpose of the study is to report the long-term efficacy of patients with neovascular age-related macular degeneration (nAMD) treated with antivascular endothelial growth factor (VEGF) in Changhua Christian Hospital in Taiwan. MATERIALS AND METHODS: Retrospective case series of patients with nAMD who were treated with intravitreal injection (IVI) of anti-VEGF and had a minimum follow-up of 48 months. Every patient was initially treated with three loading doses of either bevacizumab or ranibizumab, followed by a loose treat and extend regimen. Eyes were divided into two groups according to whether aflibercept was later used as a rescue therapy (Group 2) or not (Group 1). Patients underwent best-corrected visual acuity (BCVA) testing, optical coherence tomography, and ophthalmic examination at baseline and all the scheduled follow-up visits. RESULTS: Seventy eyes in 63 patients were included (mean age 70.54 ± 9.18 years). The mean number of IVIs per year was 5.28 ± 1.36. The mean BCVA in logarithm of the minimal angle of resolution (logMar) improved from 0.89 ± 0.45 to 0.72 ± 0.49 for all patients (P = 0.004). Significant visual improvement was noted in Group 1 (P = 0.01) at 4 years of follow-up, but not in Group 2 (P = 0.16). Patients with initial poor BCVA (LogMar visual acuity >1.0), and older age (>70 years) had significant visual improvement, in contrast to no significant visual changes in patients with younger age and initial better BCVA. CONCLUSION: Under a loose treat and extend protocol and rescue therapy of aflibercept, BCVA improvement was maintained for 4 years in patients with nAMD, especially in the older population (Registration Number: NCT03324542).
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Treatment outcomes of zone 1 retinopathy of prematurity: A study from a tertiary eye care center in South India p. 255
Parveen Sen, Sharanya Abraham, Smriti Jain, Lingam Gopal, Pramod Bhende
DOI:10.4103/tjo.tjo_62_18  
PURPOSE: The main purpose is to study the treatment outcomes of zone 1 retinopathy of prematurity (ROP). MATERIALS AND METHODS: A retrospective analysis was done of infants diagnosed with zone 1 ROP with any stage with or without plus disease who were treated with either laser photocoagulation and/or intravitreal injection of antivascular endothelial growth factor (anti-VEGF) agents and/or underwent surgery according to their stage at presentation. The retinal outcome at the final visit was analyzed. A favorable outcome was characterized by an attached retina at the posterior pole with regression of ROP (regression of plus disease as well as new vessels) while an unfavorable outcome was detached retina at posterior pole in spite of treatment. RESULTS: Seventy-eight eyes of 39 infants presented with zone 1 ROP in various stages with plus disease in 50% cases. About 60 eyes underwent treatment. Forty eyes (66.6%) had an attached retina at the final follow-up. Thirty-three eyes (55%) underwent monotherapy with 14 eyes (23.3%) showing regression of ROP with laser alone. Nineteen (31.6%) eyes were treated only by surgery. Of these, a favorable outcome was seen in four eyes (44.4%) with Stage 4 disease and three eyes (30%) with Stage 5 disease. None of the eyes received anti-VEGF as monotherapy. A combination of two or more modalities was required in the remaining 27 eyes (45%). Six eyes (10%) needed anti-VEGF injections in addition to laser and six eyes needed surgery in addition to laser to achieve a favorable outcome. Six eyes (10%) required surgery in addition to both laser and anti-VEGF therapy, and one eye (1.6%) required surgery in addition to anti-VEGF therapy for a favorable final outcome. Among the eyes undergoing treatment, 66.6% had a favorable outcome with 92.9% of eyes in Stage 3, 59% in Stage 4, and 33% in Stage 5 showing regression of disease and attached retina. CONCLUSION: In spite of the aggressive nature of zone 1 ROP, favorable outcome is possible as was seen in 66.6% of our cases. A multipronged approach using a combination of laser, intravitreal anti-VEGF agents with or without surgery may be necessary for the management of these eyes.
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Histopathologic findings after selective ophthalmic arterial injection of melphalan for retinoblastoma p. 262
Ho-Min Chen, Sherine Jue Ong, An-Ning Chao, Kuan-Lyin Liou, Shih-Ming Jung, Ling-Yuh Kao
DOI:10.4103/tjo.tjo_119_18  
PURPOSE: The aim is to describe histopathologic observations in eyes enucleated after selective ophthalmic arterial injection (SOAI) of melphalan for retinoblastoma (RB). STUDY DESIGN: This is retrospective clinical study. PATIENTS AND METHODS: Histopathologic analysis of 14 eyes (13 patients) from May 2008 through January 2015 at Chang Gung Memorial Hospital. RESULTS: The eyes after SOAI were enucleated due to tumor viability (n = 7, 2 with vitreous hemorrhage), neovascular glaucoma (n = 4), lens drop to vitreous with total hyphema and elevated intraocular pressure (n = 1), retinal detachment (RD) progressed (n = 1), and persistent RD with phthisis change (n = 1). Almost all of the eyes showed vitreous seeding (n = 11 eyes) before treatment. After the treatment of SOAI, the histopathological examination revealed complete regression in four eyes with one was clinically diagnosed as viable tumor and progression, one with RD progression, and two as neovascular glaucoma. Six eyes showed invasion into the optic nerves, reaching the lamina cribrosa in five eyes, and six eyes with invasion into the choroid were observed. All of the cases with lamina cribrosa involvement showed tumor progression before enucleation, four cases with lamina cribrosa involvement expired later. CONCLUSION: Although some cases of RB can be controlled effectively with SOAI, but for refractory cases after SOAI, earlier decision of enucleation may be needed.
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CASE REPORTS Top

Photoreceptor stretching: An optical coherence tomography finding in a case of incomplete Vogt–Koyanagi–Harada disease p. 267
Carlos Mario Pinilla-Gomez, Francisco José Rodríguez-Alvira
DOI:10.4103/tjo.tjo_70_19  
The aim of the study was to describe an optical coherence tomography finding in Vogt–Koyanagi–Harada (VKH) disease and discuss its physiopathology. A 34-year-old Hispanic male was referred to the retina clinic, with 2 weeks of “drowsiness,” headache, photopsia, and blurred vision. He was diagnosed with incomplete VKH. Optical coherence tomography, among other studies, was obtained, and a focal separation of the photoreceptor outer segments (OSs) from the inner neuroepithelium was observed. Here, we report a rare finding associated with VKH disease, which we called photoreceptor stretching and hypothesize it results from the presence of a spot of strong adherence between the OS of the photoreceptors and the retinal pigment epithelium.
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Ocular syphilis mimicking Vogt–Koyanagi–Harada disease p. 271
Yu-Ching Lin, Kang-Jung Lo, Shih-Jen Chen, De-Kuang Hwang
DOI:10.4103/tjo.tjo_63_19  
The study aimed to present a case of ocular syphilis mimicking Vogt–Koyanagi–Harada (VKH) disease. This is an observational case report. A 59-year-old female with Sicca syndrome and rheumatoid arthritis presented to the ophthalmologic department with blurred vision of the right eye for 5 days accompanied by color sensation loss in both eyes. Bilateral disc hyperemia and serous retinal detachment at the posterior pole were noted in her both eyes by fundus examination. Fluorescein angiography revealed bilateral late dye leakage from the disc and posterior choroid. Optical coherence tomography showed bilateral subretinal fluid and choroidal thickening. The impression of her condition was VKH disease initially. However, she was later diagnosed with bilateral ocular syphilis with optic neuritis which was proved by laboratory data. After appropriate antimicrobial agent treatment, her best-corrected visual acuity, serous retinal detachment, and disc hyperemia improved. There was no recurrent intraocular inflammation even without systemic steroid or immunosuppressive therapy control during the following 1 year. Ocular syphilis can mimic many other ocular inflammatory diseases including VKH disease. It is necessary to differentiate infectious causes from inflammatory origins due to the substantially different treatment and prognosis.
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Spectral-domain optical coherence tomography finding of acute retinal pigment epitheliitis p. 276
Yi-Hsuan Li, Yo-Chen Chang, Wen-Chuan Wu
DOI:10.4103/tjo.tjo_23_19  
Acute retinal pigment epitheliitis (ARPE) is a rare, transient macular disorder affecting healthy young adults. We describe the morphologic appearance of the retina by spectral-domain optical coherence tomography (SD-OCT) and to evaluate both the anatomic changes and the functional visual acuity changes over time in the course of disease. A 35-year-old healthy male presented with 1-week history of sudden-onset bilateral central scotoma with blurry vision. He denied trauma, excessive sun exposure, or drug abuse history or alkyl nitrites before. The medical and ocular examinations were unremarkable. The best-corrected visual acuity (BCVA) was 20/200 (OU) at the initial visit. Slit-lamp examination result was normal. Fundus examination revealed subfoveal yellowish lesions with a halo-like pigment in both eyes. The SD-OCT imaging showed subtle disruption of the retinal pigment epithelium (RPE) and abnormal hyperreflectivity throughout the full thickness of the foveola in both eyes. Six weeks later, the BCVA improved to 20/30 (OU) without any treatment. Six months later, the BCVA observed deteriorated to 20/50 (OU). SD-OCT demonstrated ellipsoid zone and cone outer segment tips line defects at the fovea with sharply defined borders. One year later from the initial visit, the BCVA improved to 20/20 (OU), but persisted macular microhole presents on the SD-OCT. The patient was followed for 1 year without any treatment. Thereafter, we noted that in the case of poor initial visual acuity, external limiting membrane, or outer nuclear layer involvement, as determined by SD-OCT, at the baseline might need longer time for visual acuity. The natural course of ARPE may involve the demonstration of a minor outer retinal defect that is similar to a macular microhole. In ARPE, like SD-OCT findings, the location of the initial lesion is the photoreceptor outer segments. It is not just limited to the RPE.
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Persistent vitreous hemorrhage after intravitreal injection of dexamethasone intravitreal implant in patients with diabetic macular edema Highly accessed article p. 280
Meng-Syuan Li, Shwu-Jiuan Sheu
DOI:10.4103/tjo.tjo_87_17  
We report three cases of persistent vitreous hemorrhage after injection of a biodegradable 0.7 mg dexamethasone intravitreal implant (Ozurdex, Allergan), (DEX) to treat and manage diabetic macular edema (DME); we also summarize available case reports and review the literature regarding persistent vitreous hemorrhage. All three patients underwent pars plana vitrectomy due to nonclearing vitreous hemorrhage after conservative treatment for 2–3 months. During operation, we noted the presence of neovascular membrane along the vascular arcade with taut posterior hyaloid; however, no posterior vitreous detachment (PVD) was found in any of three patients. The implants were carefully preserved, so were the effects in reducing macular edema. Persistent vitreous hemorrhage after DEX injection was rare but manageable without interrupting the effect on DME. Eyes with neovascular membrane but without PVD may be at risk of developing vitreous hemorrhage after DEX injection.
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Anterior transposition of inferior oblique for inferior rectus muscle aplasia p. 284
Anupam Singh, Ajai Agrawal, Sanjeev Kumar Mittal, Barun Kumar, Kartik Maheshbhai Rana, Rupal Verma
DOI:10.4103/tjo.tjo_4_18  
Congenital absence of extraocular muscle is rare. The most common extraocular muscle found to be congenitally absent is superior oblique followed by inferior rectus. Patients with absent inferior rectus muscle can present with abnormal head posture and incomitant hypertropia with limitation of ocular motility in the field of action of the inferior rectus with or without torticollis. Microphthalmos, microcornea, coloboma, and Axenfeld–Rieger syndrome are known to be commonly associated with inferior rectus muscle aplasia. Orbital computed tomography (CT) or magnetic resonance imaging before surgery is useful for confirmation of the diagnosis and plan of management. We report satisfactory surgical outcome of anterior transposition of inferior oblique in a case of inferior rectus aplasia with iris coloboma, microcornea, and anomalous insertion of inferior oblique. The patient had right hypertropia in primary position which increased on levoversion and left tilt. Preoperative orbital CT revealed congenital absence of inferior oblique. Peroperatively, congenital absence of inferior rectus was confirmed, and inferior oblique was found to be hyperplastic and abnormally inserted to the sclera. Anterior transposition of inferior oblique was done with satisfactory outcome.
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Blindness due to leptomeningeal carcinomatosis as an initial manifestation of recurrent acute lymphoblastic leukemia Highly accessed article p. 288
Ya-Chi Huang, Cyuan-Jheng Wang, Jieh-Ren Jou
DOI:10.4103/tjo.tjo_107_17  
Leptomeningeal carcinomatosis (LC) is an uncommon presentation of acute lymphoblastic leukemia (ALL), and it is a devastating and life-threatening complication. The disease affects all levels of the central nervous system, and most patients present with different multifocal neurological symptoms. This case was a 34-year-old male who had acute bilateral blindness secondary to recurrent ALL with meningeal infiltration. Diagnosis of LC is made based on the clinical symptoms and the test results including cranial and spinal magnetic resonance imaging and cerebrospinal fluid (CSF) survey. The differential diagnosis of meningeal enhancement and early treatment are also important for prognosis. This case had a good visual recovery after treatment.
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Intracameral viscoelastic treatment for hypotony after glaucoma incisional surgery p. 292
Tian Xia, Albert S Khouri
DOI:10.4103/tjo.tjo_31_18  
We report on a minimally invasive treatment of symptomatic hypotony after glaucoma surgery. Hypotony after incisional glaucoma surgery can have severe visual consequences. Refractory symptomatic hypotony often requires surgical intervention to prevent further vision loss. The clinical records of four patients in this interventional case series with symptomatic hypotony and choroidal detachments after incisional glaucoma surgery between 2013 and 2014 were reviewed. Observations were made as the cases progressed. Visual obscuration secondary to refractory hypotony was treated with an intracameral injection of high-molecular-weight ocular viscoelastic devices (HMWOVD). Postinjection, mean intraocular pressure improved from a baseline of 3.6 mm Hg to 24.0, 15.5, and 9 mm Hg at 1 day, 1 month, and 6 months' post-intervention, respectively. The mean visual acuity after injection improved from 20/274 to 20/83 at 6 months. Choroidal detachments resolved within 1 week in all patients. Intracameral HMWOVD for the treatment of symptomatic hypotony post-incisional glaucoma surgery is minimally invasive, avoided reoperation, and led to quick visual recovery.
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