The Asia-Pacific Journal of Ophthalmology

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Pioneer of Chinese Ophthalmology—130th Anniversary of Beijing Tongren Hospital Yusufu, Mayinuer; Wang, Ningli
Much has been achieved in clinical and scientific research in the past 130 years by Beijing Tongren Hospital, which has evolved from an eye clinic to a comprehensive hospital with an ophthalmology department known as one of the best in China. This article presents the most historic moments and events in the development of a hospital with the largest eye care service volume. In addition, given the leading position of Tongren, the development of ophthalmology in Tongren is also the epitome of the development of modern ophthalmology in China. Beijing Institute of Ophthalmology (BIO) was established in 1959 as an affiliated institution under Tongren, aiming at carrying out applied science and basic science research, and directors of BIO have thus far served 4 terms as president of the Chinese Ophthalmological Society. In 2002, Beijing Tongren Eye Center (hereafter referred to as the Eye Center) was established to combine all the ophthalmic resources within Tongren. In 2017, the Eye Center alone had a surgical volume of 78,223, with surgeries for cataract, refractive errors, fundus, glaucoma, and corneal disease being the 5 most common, and 902,409 outpatient visits. Equipped with the leading experts and equipment, Tongren is dedicated to the battle against major eye diseases by carrying out large population-based epidemiological surveys and basic science research on pathogenesis and effective treatments, thereby making contributions to the development of the science of ophthalmology along with the delivery of eye care services in China and beyond.

Original Study - Clinical

Sustainability of Pain Relief After Corneal Collagen Cross-Linking in Eyes With Bullous Keratopathy Ono, Takashi; Mori, Yosai; Nejima, Ryohei; Ogata, Miyuki; Minami, Keiichiro; Miyata, Kazunori
Purpose: This study aimed to examine the efficiency and sustainability of pain relief produced by corneal collagen cross-linking (CXL) in eyes with bullous keratopathy (BK) and to explore the histopathological changes in the stroma by using in vivo confocal microscopy.

Design: Prospective observational case series.

Methods: Fourteen eyes of 14 consecutive BK patients were treated with CXL with dehydration of the corneal stroma and followed up for 1 year after treatment. The best-corrected visual acuity (BCVA), intraocular pressure, and central corneal thickness (CCT) were examined before the treatments and up to 1 year after. The intensity and frequency of pain were graded on a scale from 0 (minimum) to 10 (maximum). At 1 year after CXL, the corneal stroma was observed using confocal microscopy at depths of 100 and 200 μm.

Results: The BCVA and CCT did not change significantly. The mean pain intensity and frequency scores were 5.6 and 4.6, respectively, before treatment. The intensity score significantly decreased at 1 week and onward, and the frequency score significantly decreased over 6 months after treatment. The confocal microscopy images showed that keratocytes and nerve fibers were rare and sparsely distributed in the stroma 1 year after CXL.

Conclusions: The CXL efficiently relieved pain due to BK for 1 year after treatment. The in vivo confocal microscopy observations and unchanged CCT demonstrated that the persistence of pain relief was due to the inadequate regeneration of nerve fibers in the corneal stroma.
Optical Coherence Tomography of Small Retinoblastoma Welch, R. Joel; Rao, Raksha; Gordon, Phillip S.; Say, Emil Anthony T.; Shields, Carol L.
Purpose: To investigate hand-held optical coherence tomography (HH-OCT) characteristics of small (<1 mm thickness) retinoblastoma.Design: Retrospective observational case series.Methods: Patient and tumor data were extracted from the medical record and analyzed along with HH-OCT scans. Determination of tumor layer of origin was performed using a layer-by-layer analysis of HH-OCT data and specific HH-OCT–related features were described.Results: There were 20 sub-millimeter retinoblastomas from 16 eyes of 15 patients. Mean largest tumor basal diameter by HH-OCT was
2.2 mm (median, 1.9; range, 0.7–4.1 mm), and mean tumor thickness was 468 μm (median, 441; range, 151–998 μm). In all cases, the retinoblastoma caused discontinuity or disruption of the inner nuclear (INL), outer plexiform (OPL), outer nuclear (ONL), and external limiting membrane (ELM) layers (20/20, 100%). Tumor origin was in the INL in 19/20 (95%) and equivocal (INL vs ONL) in 1/20 (5%). Intratumoral microcalcification was present in 14/20 tumors (70%). There were 2 characteristic findings (signs) on HH-OCT including the INL “fish tail” sign with splaying of the INL at the tumor margin (19/20, 95%) and the ONL “shark fin” sign with folding of the ONL and OPL, conforming to the lateral tumor margins (15/20, 75%). Both signs were concurrently present in 15 tumors (15/20, 75%).Conclusions: HH-OCT demonstrated that sub-millimeter retinoblastoma seems to originate from the INL, with tumor base and thickness growth progressing in a linear relationship. Characteristic HH-OCT findings included intratumoral microcalcification, INL “fish tail” sign, and ONL “shark fin” sign.
Anesthesia Considerations in Modified Osteo-Odonto-Keratoprosthesis Raman, Sonali; Singh, Sumeer; Jagdish, V.
Purpose: The purpose of this study was to elucidate anesthesia-related challenges in 74 cases who underwent modified osteo-odonto-keratoprosthesis (MOOKP).

Design: Retrospective cohort study.

Methods: Medical records of 74 consecutive patients who underwent MOOKP surgery between January 2007 and January 2015 were studied. Data such as demographic details, systemic comorbidities, indications for MOOKP, anesthesia techniques, and postoperative events in various stages of MOOKP were collected and analyzed.

Results: The mean age of the patients was 29.7 ± 9.13 years. Of the 74 patients, 47 were men. The most common indication for MOOKP was found to be Stevens–Johnson syndrome (53%) followed by chemical injury (38%). In all stages of the MOOKP procedure, 94.6% of cases were found to have American Society of Anesthesiologists (ASA) score grade II, whereas 4.6% had grade III. Mallampati score of 1 was found in 79.7% of cases in stage 1, 82.4% of cases in stage 1B + 1C, and 81% of cases in stage 2. Recovery grade of 10 was noted in all the cases at all stages of the MOOKP procedure. Intubation in the second attempt was carried out in 8 cases and oral intubation in stage 1B + 1C was performed in 4 cases. Difficulty in intubation was noted in 3 cases in stage 1A, 4 cases in stage 1B + 1C, and 1 case in stage 2.

Conclusions: In patients undergoing MOOKP, a good preanesthetic evaluation and intraoperative anesthesia plan before each stage could help in successful administration of anesthesia in these patients.
Leaving No One Behind: Strengthening Access to Eye Health Programs for People With Disabilities in 6 Low- and Middle-Income Countries Mörchen, Manfred; Bush, Asahel; Kiel, Petra; Lewis, David; Qureshi, Babar
Purpose: To assess the impact of inclusive eye health programs for people with disabilities.

Design: A synthesis evaluation study.

Methods: A cross-disciplinary team of ophthalmologists, evaluation, and disability-inclusive development advisors purposively selected evaluation reports of CBM-supported inclusive eye health programs in low- and middle-income countries. Employing a change-promoting paradigm, salient achievements and challenges were narratively analyzed and recommendations suggested based on a previously developed framework for strengthening disability inclusion in eye health programs.

Results: Evaluations from 10 programs implemented in 6 countries (Cambodia, Egypt, Ethiopia, Indonesia, Pakistan, Vietnam) from 2011 to 2016 were identified. Training of medical staff and government officials resulted in increased awareness about disability rights and improved physical accessibility of eye health facilities. Relevant information about inclusion in eye health was incorporated in national eye health training curricula in some countries. Information, education, and communication material about eye health neglected patients with hearing and learning impairments. An overly narrow focus on disability inclusion confounded intersectoral barriers to eye health services. Collaboration of eye health staff with disability peoples organizations improved significantly but evidence of its impact was elusive. Collection of disability-disaggregated data posed significant challenges and made it difficult to demonstrate increased access to eye health programs by people with disabilities.

Conclusions: Introduction of disability inclusion in eye health systems of countries with limited resources poses significant challenges. Future programs striving to improve access to eye health services for marginalized populations including people with disabilities might consider more flexible and contextualized approaches.
Blindness and Visual Impairment Profile and Rapid Assessment of Avoidable Blindness in South East Asia: Analysis of New Data. 2017 APAO Holmes Lecture. Das, Taraprasad
Purpose: The International Agency for Prevention of Blindness (IAPB) South East Asia region (SEAR) that consists of 11 countries contains 26% of the world’s population (1,761,000,000). In this region 12 million are blind and 78.5 million are visually impaired. This amounts to 30% of global blindness and 32% of global visual impairment.
Design: Rapid assessment of avoidable blindness (RAAB) survey analysis.
Methods: RAAB, either a repeat or a first time survey, was completed in 8 countries in this decade (2010 onwards). These include Bangladesh, Bhutan, India, Indonesia, Maldives, Sri Lanka, Thailand, and Timor Leste.
Results: Cataract is the principal cause of blindness and severe visual impairment in all countries. Refractive error is the principal cause of moderate visual impairment in 4 countries: Bangladesh, India, Maldives, and Sri Lanka; cataract continues to be the principal cause of moderate visual impairment in 4 other countries: Bhutan, Indonesia, Thailand, and Timor Leste. Outcome of cataract surgery is suboptimal in the Maldives and Timor Leste.
Conclusions: Rigorous focus is necessary to improve cataract surgery outcomes and correction of refractive error without neglecting the quality of care. At the same time allowances must be made for care of the emerging causes of visual impairment and blindness such as glaucoma and posterior segment disorders, particularly diabetic retinopathy.
First Rapid Assessment of Avoidable Blindness Survey in the Maldives: Prevalence and Causes of Blindness and Cataract Surgery Thoufeeq, Ubeydulla; Das, Taraprasad; Limburg, Hans; Maitra; Maharshi; Panda, Lapam; Sil, Asim; Trevelyan John; Sapkota, Yuddha
Purpose: A nationwide rapid assessment of avoidable blindness survey was undertaken in the Maldives among people aged 50 years or more to assess the prevalence and causes of blindness and visual impairment, cataract surgical coverage, cataract surgery outcome, and barriers to uptake of cataract surgical services.

Design: Prospective population-based study.

Methods: In the cluster sampling probability proportionate to size method, 3100 participants in 62 clusters across all 20 atolls were enrolled through house-to-house visits. They were examined in clusters by an ophthalmologist-led team. Data was recorded in mRAAB version 1.25 software on a smartphone.

Results: The age-sex standardized prevalence of blindness was 2.0% [95% confidence interval (CI), 1.5-2.6]. Cataract was the leading cause of blindness (51.4%) and uncorrected refractive error was the leading cause of visual impairment (50.9%). Blindness was more prevalent in higher age groups and women (16.3%). Cataract surgical coverage was 86% in cataract blind eyes and 93.5% in cataract blind persons. Good visual outcome in cataract operated eyes was 67.9% (presenting) and 76.6% (best corrected visual acuity). In this study, 48.1% of people had received cataract surgery in neighboring countries. Important barriers for not using the services were “did not feel the need” (29.7%) and “treatment deferred” (33.3%).

Conclusions: Cataract surgical coverage is good, though nearly half the people received surgery outside the Maldives. Cataract surgery outcomes are below World Health Organization standards. Some barriers could be overcome with additional human resources and training to improve cataract surgical outcomes, which could encourage greater uptake of services within the country.
Predictive Value of Baseline Biochemical Parameters for Clinical Response of Macular Edema to Bevacizumab in Eyes With Central Retinal Vein Occlusion: A Retrospective Analysis Madanagopalan, V.G.; Kumari, Bibha
Purpose: To evaluate the influence of baseline biochemical parameters on the improvement in best corrected visual acuity (BCVA) and reduction in central foveal thickness (CFT) in patients treated with intravitreal bevacizumab (IVB; Avastin, Genentech, Inc) for macular edema (ME) secondary to central retinal vein occlusion (CRVO).

Design: A retrospective study.

Methods: Seventy eyes of 70 participants with CRVO who underwent IVB for ME and had at least 1 month of follow-up after the last injection were studied. Demographic variables, systolic and diastolic blood pressure (SBP and DBP), BCVA, CFT measured by optical coherence tomography (OCT), and biochemical investigations [hemoglobin, fasting and postprandial blood sugar (FBS and PPBS), lipid profile, blood urea (BU), serum creatinine (SC), glycosylated hemoglobin (HbA1c)] at baseline were noted. IVB need at every visit was based on clinical and OCT parameters. Changes in BCVA (ΔBCVA) and CFT (ΔCFT) from baseline to last injection were estimated.

Results: After IVB, there was a statistically significant reduction in mean CFT (P < 0.01). The group of patients with normal BU and SC had more than 2 lines of improvement compared with those with elevated values (P = 0.043 and 0.009, respectively). Other parameters like FBS, PPBS, hemoglobin, HbA1c, and serum lipids were not associated with improvement of BCVA and reduction of CFT.

Conclusions: Normal baseline renal parameters (BU and SC) predict better visual outcome after treatment for ME in CRVO and offer additional benefit over and above that obtained with ME reduction.

Review Article

Leber Hereditary Optic Neuropathy—Light at the End of the Tunnel? Kim, Ungsoo Samuel; Jurkute, Neringa; Yu-Wai-Man, Patrick
Leber hereditary optic neuropathy (LHON) is an important cause of mitochondrial blindness. The majority of patients harbor one of three mitochondrial DNA (mtDNA) point mutations, m.3460G>A, m.11778G>A, and m.14484T>C, which all affect complex I subunits of the mitochondrial respiratory chain. The loss of retinal ganglion cells in LHON is thought to arise from a combination of impaired mitochondrial oxidative phosphorylation resulting in decreased adenosine triphosphate (ATP) production and increased levels of reactive oxygen species. Treatment options for LHON remain limited, but major advances in mitochondrial neuroprotection, gene therapy, and the prevention of transmission of pathogenic mtDNA mutations will hopefully translate into tangible benefits for patients affected by this condition and their families.
The Role of Optical Coherence Tomography in Differentiating Optic Disc Drusen from Optic Disc Edema Costello, Fiona; Malmqvist, Lasse; Hamann, Steffen
An elevated optic nerve head can be an ominous sign, sometimes signifying an underlying basis for raised intracranial pressure. Alternatively, patients may harbor a different mechanism for this optic nerve head appearance, including optic disc drusen (ODD), which does not confer any life-threatening implications. It is important to refine
the approach to distinguishing ODD from papilledema because this is a relatively common, and important, conundrum encountered in clinical practice. Optical coherence tomography (OCT) is a noninvasive, readily accessible, and cost-effective ocular imaging technique that can improve the diagnostic accuracy for detecting ODD; or, instead, increase the index of suspicion for papilledema, thus prompting additional investigations
needed to identify (or exclude) potential causes of raised intracranial pressure. In this review, we will discuss the value of OCT in the diagnostic approach to cases of mild optic disc elevation, with acknowledgment of the potential pearls and pitfalls of this imaging technology. In particular, we will emphasize the helpful role OCT can play in differentiating cases of ODD from mild papilledema in the context of idiopathic intracranial hypertension (IIH).
Use of Noninvasive Imaging in Giant Cell Arteritis Halbach, Caroline; McClelland, Collin M.; Chen, John; Li, Suellen; Lee, Michael S.
Giant cell arteritis (GCA) requires a prompt diagnosis to avoid significant morbidity among the elderly. An accurate diagnosis is also paramount given the side effect profile of long-term corticosteroid treatment. Temporal artery biopsy (TAB) has long remained the gold standard for the diagnosis of GCA but requires an invasive procedure that is not without risk. This article discusses the argument for and against the use of noninvasive imaging including ultrasound, magnetic resonance imaging, and positron emission tomography scanning for the diagnosis of GCA. It also provides a suggested diagnostic algorithm for when to consider noninvasive imaging versus TAB.
Steroid Treatment of Optic Neuropathies Stunkel, Leanne; Van Stavern, Gregory P.
The etiologies of optic neuropathy include inflammation, ischemia, toxic and metabolic injury, genetic disease, and trauma. There is little controversy over the practice of using steroids in the treatment of optic neuritis—it is well established that intravenous steroid treatment can speed visual recovery but does not alter final visual function. However, there is controversy surrounding the acceptable routes of administration, dosage, and course of treatment. Additionally, the typical patient with optic neuritis is young and otherwise healthy, and thus is likely to tolerate steroids well. In ischemic and traumatic causes of optic neuropathies, the initial injury is not inflammatory, but damage may be compounded by secondary injury due to resultant inflammation and swelling in the confined space of the optic canal. Steroids have been considered as a means of minimizing inflammation and swelling, and thus minimizing the secondary injury that results. However, the use of steroids in traumatic and ischemic optic neuropathies is highly controversial—the evidence for the efficacy of treatment with steroids is insufficient to show that there is significant benefit. Additionally, patients with these conditions are more likely to have comorbidities that make them vulnerable to significant adverse events with the use of steroids. In this article, we attempt to analyze the current state of the literature regarding the use of steroids in the treatment of optic neuropathies, specifically optic neuritis, nonarteritic anterior ischemic optic neuropathy, and traumatic optic neuropathy.
The Role of Optical Coherence Tomography in the Acute Management of Neuro-Ophthalmic Diseases Chan, Noel C.Y.; Chan, Carmen K.M.
Optical coherence tomography (OCT) can provide highspeed and high-resolution images of the anatomical structures of the optic nerve head and macula. However, in neuro-ophthalmic conditions that present acutely, structural changes lag functional deficits, and the role of OCT in the acute setting has been challenged. This review aims to summarize the recent literature and evidence supporting the use of OCT in the acute management of some common neuro-ophthalmic scenarios, including the differential diagnosis of optic disc swelling, and in patients with suspected papilledema, optic neuritis, ischemic optic neuropathies, and Leber hereditary optic neuropathy. The limitations of OCT are also discussed.
Neuromyelitis Optica: Review and Utility of Testing Aquaporin-4 Antibody in Typical Optic Neuritis Seay, Meagan; Rucker, Janet C.
Neuromyelitis optica (NMO) is an autoimmune, inflammatory demyelinating disorder often leading to severe vision impairment and disability. The discovery of a diagnostic biomarker, the aquaporin-4 antibody (AQP4-IgG), transformed the clinical diagnosis and treatment of NMO and broadened the spectrum of disease [NMO spectrum disorders (NMOSD)]. Though the antibody is highly sensitive and specific to NMOSD, routine testing in patients with typical optic neuritis is considered controversial. This article will provide a brief review of NMOSD and highlight the pros and cons of routine testing in typical optic neuritis.
Treatment of Nonarteritic Acute Central Retinal Artery Occlusion Sharma, Rahul A.; Dattilo, Michael; Newman, Nancy J.; Biousse, Valerie
Central retinal artery occlusion (CRAO) is an event most often caused by an embolus originating in the ipsilateral carotid artery, aortic arch, or heart. CRAO may result from partial or complete occlusion of the central retinal artery (CRA), which acts as the primary blood supply to the inner neurosensory retina, and typically results in profound vision loss and permanent visual disability. No consensus has emerged regarding the optimal treatment of CRAO. All proposed treatments are of questionable efficacy and many have uncertain risk profiles. In certain circumstances, thrombolysis may be attempted as a treatment option; however, the evidence to support broad use of thrombolytics in the treatment of acute CRAO remains elusive. It is known that the risk factors that predispose to other cardiovascular and cerebrovascular events are often present in CRAO. Accordingly, identification of patients at highest risk of stroke and secondary prevention of ischemic events remains the primary focus of management. This review offers a summary of the clinical presentation, diagnosis, and prognosis of CRAO, with an emphasis on treatment options.
Updates and Controversies in the Management of Acute Optic Neuritis Meltzer, Ethan; Prasad, Sashank
Optic neuritis remains a common diagnosis with controversial management. Although typical optic neuritis is often associated with “good” recovery of visual acuity, patients are often left with persistent impairments of contrast sensitivity, color vision, and visual field. These permanent visual deficits correlate with structural injury to the anterior visual pathway and are closely linked to visual quality of life. High dose corticosteroids are commonly used for patients with acute optic neuritis. However, even several decades after the initial clinical trials, there remains significant controversy regarding the efficacy and utility of this treatment. There is a need for more effective treatments, and many new immunomodulatory and neuroprotective agents have been investigated recently. Atypical optic neuritis, such as that seen with neuromyelitis optica spectrum disorder, often requires more aggressive initial treatment. Thus, it is important for clinicians to have a framework for rapid diagnosis and triage of patients who present with typical or atypical optic neuritis. Lastly, optic neuritis is associated with an elevated long-term risk of developing multiple sclerosis. Some patients may benefit from initiation of medications targeting multiple sclerosis at the time of initial presentation of optic neuritis. Appropriate identification and treatment of patients at highest risk of developing multiple sclerosis may help impact their disease course, while limiting exposure to potential adverse effects in patients who are at lower risk and do not require disease-modifying treatment.
Vascular Anomalies of the Orbit—A Reappraisal Sullivan, Timothy John
The recent International Society for the Study of Vascular Anomalies (ISSVA) classification of vascular anomalies can be applied to orbital lesions, dividing them into vascular tumors and vascular malformations. Orbital cavernous hemangiomas are probably best considered cavernous venous malformations under this classification. Management of symptomatic lesions can be with surgical excision or stereotactic fractionated radiotherapy in selected cases. Beta-blockers including propranolol and topical timolol maleate represent first-line therapy for infantile hemangiomas, although surgery has a role in selected cases. Orbital venous-lymphatic malformations are problematic but with improved imaging, neuroradiological intervention, and a multidisciplinary approach to management, outcomes are improving.
Visual Evoked Potentials and Glaucoma Tai, Tak Yee Tania
Visual evoked potentials (VEP) can be used to assess the function of the visual system objectively. Research on VEP testing as a method of glaucoma evaluation has been performed for many years. Pattern VEP has shown good specificity and sensitivity in the detection of glaucoma in some studies, but other studies have not shown similar efficacy. Multifocal VEP can produce a topographical measure of glaucomatous damage and has been shown to be able to detect a similar number of defects in patients with glaucoma or ocular hypertension as compared with the visual field test. Despite promising data on these VEP test modalities in the assessment of glaucoma, multiple aspects of test administration make their routine use impractical in a clinical setting. New VEP testing modalities, such as short-duration transient VEP and isolated-check VEP, allow the test to be performed more quickly and easily. Further research on these more recent technologies may allow us to use VEP effectively in the diagnosis and management of glaucoma.
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