The Asia-Pacific Journal of Ophthalmology

Editorial

Anti-VEGF and Other Therapies for Macular Edema due to Central Retinal Vein Occlusions Jonas, Jost B.
In their meta-analysis of the current outcomes of anti–vascular endothelial growth factor (VEGF) therapy in the treatment of macular edema secondary to central retinal vein occlusions (CRVOs), Spooner et al1 reported that the anti-VEGF therapy is effective for improving the vision prognosis of CRVO with a good safety record. The results of this meta-analysis agree with previous multicenter randomized controlled trials, recent surveys of the current literature, and other investigations.
Artificial Intelligence in Ophthalmology: Accuracy, Challenges, and Clinical Application Tan, Zachary; Scheetz, Jane; He, Mingguang
Artificial intelligence (AI) technologies promise a revolution in the way we prevent, diagnose, and manage disease. The potential for AI to transform medicine is increasingly becoming part of popular discourse, although the origin of these technologies can be traced back to Alan Turing’s research in the 1930s. The term “artificial intelligence” was first coined by John McCarthy in 1955 to describe the science of creating intelligent machines which replicate human behavior. It has many subtypes and modern examples include machine learning (ML), which learns automatically from data sets in the absence of explicitly programmed rules. A subset of ML is deep learning (DL), which trains itself using multiple layers of neural networks which are adaptable programming units inspired by the structure of human neurons.

Original Study - Clinical

Visual Outcomes Following Intravitreal Ranibizumab for Diabetic Macular Edema in a Pro Re Nata Protocol from Baseline: A Real-World Experience James, Datta G.P.; Mitkute, Doville; Porter, Grazyna; Vayalambrone, Deepak
Purpose: To investigate long-term outcomes of pro re nata (PRN) treatment protocol of ranibizumab for diabetic macular edema (DME) adopted from the first month of therapy without 3 loading doses.
Design: Retrospective interventional study.
Methods: We analyzed 180 eyes of 144 patients treated with ranibizumab for DME with a minimum follow-up of 1 year during December 2013 to December 2017. Data of all patients with treatment-naive center-involving DME who received at least 1 intravitreal injection of ranibizumab during the study period were drawn from a locally adapted electronic form for DME. The primary outcome measure was change in best-corrected visual acuity (BCVA) from baseline at 1-year follow-up, with intergroup comparisons in BCVA between eyes receiving 1, 2, and 3 injections in the first 3 months of treatment.
Results: The mean baseline BCVA was 0.47 ± 0.30 logMAR, which improved to 0.38 ± 0.3 logMAR (P = 0.003) at 3 months and stabilized at 0.35 ± 0.27 logMAR at 1 year (P = 0.46 vs BCVA at 3 months) and 0.34 ± 0.26 logMAR at 2 years of follow-up (P = 0.44 vs BCVA at 3 months). At 3 months, 24 eyes (13%) underwent 1 intravitreal injection, 52 eyes (29%) had 2 injections, and the majority (n = 104 eyes, 58%) had 3 injections on a monthly basis. During the first year, the group that received only 1 injection in the first 3 months also required fewer injections and fewer follow-up visits compared with those receiving 2 or 3 injections in the first 3 months.
Conclusions: One-third of eyes with DME responded well to PRN treatment strategy from the first month without 3 loading doses of ranibizumab. Baseline visual acuity is the best predictor of vision at 1 and 2 years of follow-up.
Clinical Course and Treatment Response of Neuromyelitis Optica Spectrum Disease: An 8-Year Experience Lin, Chao-Wen; Lin, I-Hung; Chen, Ta-Ching; Jou, Jieh-Ren; Woung, Lin-Chung
Purpose: To report the clinical course and treatment response in a cohort of patients with neuromyelitis optica spectrum disorder (NMOSD) from a single referral center in Taiwan.
Design: Case series.
Methods: All NMOSD patients who received treatment and follow-up checks at National Taiwan University Hospital for at least 2 years between January 2008 and December 2016 were recruited. Demographic data and detailed characteristics of clinical course including acute episodes, maintenance therapies, and visual outcome were collected. Patients were examined every 6 months and during each episode of relapse.
Results: A total of 96 patients were identified; of them, 68 (70.8%) had optic neuritis. Optic neuritis was the initial presentation of NMOSD in 44 patients. Among the patients with optic neuritis, 32.4% had recurrent optic neuritis within 1 year from the first episode. Compared with the group without optic neuritis, the group with optic neuritis had a younger age of presentation (34.4 ± 15.9 vs 42.4 ± 14.8 years, P = 0.02) and a higher 1-year recurrence rate (64.7% vs 17.9%, P < 0.001). Among the patients with optic neuritis, 51.5% had a final visual acuity of worse than 20/200. Multiple regression analysis showed that the presence of aquaporin-4-IgG antibodies and poor initial visual acuity were the risk factors for worse visual outcome.
Conclusions: In this study, patients with optic neuritis were younger and had a higher 1-year recurrence rate. Despite using steroid therapy during the acute phase and immunosuppressive agents as long-term treatment, visual prognosis was poor. Aquaporin-4-IgG antibodies and initial visual acuity were associated with final visual outcome.
Intra-Arterial Chemotherapy for Retinoblastoma: 8-Year Experience from a Tertiary Referral Institute in Thailand Rojanaporn, Duangnate; Chanthanaphak, Ekachat; Boonyaopas, Rawi; Sujirakul, Tharikarn ; Hongeng, Suradej; Ayudhaya, Sirintara Singhara Na
Purpose: To study the safety and efficacy of intra-arterial chemotherapy (IAC) as a treatment for intraocular retinoblastoma in Thailand.
Design: Retrospective, interventional case series.
Methods: In this study, IAC was performed as primary or secondary treatment for patients with intraocular retinoblastoma using melphalan with or without additional topotecan or carboplatin. Survival rate, globe salvage rate, and treatment complications were recorded and analyzed.
Results: Of 27 eyes of 26 patients with retinoblastoma, 7 (26%) had IAC as primary treatment and 20 (74%) had IAC as secondary treatment. The eyes were classified by International Classification of Retinoblastoma (ICRB) as group B (n = 3, 11%), group C (n = 1, 4%), group D (n = 12, 44%), and group E (n = 11, 41%). Catheterization was successful in 75 (94%) of 80 sessions. The median number of IAC sessions was 3 (range, 1–7). At a mean follow-up of 32 months (range, 3–95 months), the overall globe salvage rate was 52%, with 100% in groups B and C, 75% in group D, and 9% in group E. Complications of IAC included occlusive vasculopathy (n = 4, 15%), vitreous hemorrhage (n = 3, 11%), retinal artery precipitation (n = 2, 7%), strabismus (n = 2, 7%), and transient ischemic attack (n = 1, 4%). The overall survival rate was 96% (n = 25).
Conclusion: Our experience suggests that IAC is a safe and effective treatment for patients with ICRB group B, C, D, and some group E retinoblastoma. Careful patient selection and experienced surgeons are critical for achieving the best treatment outcome.
Bilateral Symmetric and Asymmetric Superior Rectus Recession for Patients with Dissociated Vertical Deviation Tibrewal, Shailja; Nguyen, Phuong T.T.; Ganesh, Suma; Molinari, Andrea
Purpose: To evaluate the outcome of bilateral symmetric and asymmetric superior rectus (SR) recessions in patients with bilateral dissociated vertical deviation (DVD) without oblique dysfunction and determine factors that might influence the surgical outcome.
Design: Retrospective study.
Methods: All patients who underwent bilateral SR recession for bilateral DVD from January 2012 to December 2016 at an eye hospital in New Delhi, India were included. Indication for surgery was decompensated DVD in 1 or both eyes. Symmetric SR recession was performed for symmetric DVD and asymmetric SR recession was performed for asymmetric DVD of 10 prism diopters (PD) or more. Patients with a minimum follow-up of 6 months were included. Success was defined as absence of manifest DVD in both eyes at the final postoperative visit.
Results: Medical records of 27 patients were analyzed. Their median age at surgery was 8 years [interquartile range (IQR), 6–10 years] and mean follow-up was 16.3 months (range, 6–48 months). Symmetric and asymmetric surgeries were performed in 19 and 8 patients, respectively. The amount of SR recession performed ranged from 5 to 10 mm. The median DVD reduced from 9 PD (IQR, 6–14 PD) to 5 PD (IQR, 3–8 PD) in the right eye (P = 0.015) and 9 PD (IQR, 7–12 PD) to 6 PD (IQR, 3–10 PD) in the left eye (P = 0.016) after surgery. Successful outcome was seen in 63% of patients. There was no difference in successful outcome with respect to age, sex, preoperative horizontal deviation, preoperative vertical deviation, postoperative residual horizontal deviation, surgical technique, asymmetry of SR recession, and magnitude of preoperative DVD. Patients with a preference for fixation were more likely to have a successful outcome.
Conclusions: Bilateral SR recession resulted in a success rate of 63% after single operation for bilateral DVD without oblique dysfunction. We found that the probability of a successful outcome did not depend on age at surgery, sex, preoperative horizontal or vertical deviation, magnitude of preoperative DVD, symmetry of SR recession, or surgical technique.
The Relationship Between Optic Disc Parameters and Female Reproductive Factors in Young Women Lee, Samantha S.Y.; Yazar, Seyhan; Pasquale, Louis R.; Sanfilippo, Paul G.; Hewitt, Alex W.; Hickey, Martha; Skinner, Rachel; Mackey, David A.
Purpose: It has been suggested that female sex steroids have neuroprotective properties that may reduce risk of glaucoma in premenopausal women. In this study, we explored the associations of optic disc measures with female reproductive factors in a population of young women.
Design: Cohort study.
Methods: Young women (n = 494; age range, 18–22 years) were recruited as part of the Western Australian Pregnancy Cohort (Raine) Study. Information on age at menarche, parity, and use of hormonal contraceptives were obtained from questionnaires. Participants underwent an eye examination, including spectral-domain optical coherence tomography imaging, to obtain optic disc parameters.
Results: Women who had given birth at least once (parous women; n = 10) had larger vertical neuroretinal rim widths (P < 0.001) than nulliparous women (n = 484) after correcting for use of hormonal contraceptives, intraocular pressure, refractive error, and family history of glaucoma. Furthermore, vertical and horizontal cup-to-disc ratios, which are inherently related to neuroretinal rim width, were found to be smaller among parous women compared with nulliparous women (both
P < 0.001). Age at menarche and use of hormonal contraceptives were not significantly associated with any optic disc parameters.
Conclusions: We found limited evidence that female reproductive factors were related with optic disc parameters during young adulthood. The association between parity and optic disc parameter, though significant, should be further investigated given the small number of parous women in the current sample. Future follow-ups of this cohort will allow us to explore any associations of these factors with optic disc parameters and glaucoma risk at an older age.
Comparison of Icare Rebound Tonometer and Perkins Applanation Tonometer in Community Eye Screening Ting, Siew Leng; Lim, Lik Thai; Ooi, Chor Yau; Rahman, Md Mizanur
Purpose: To compare the measurement of intraocular pressure (IOP) of Icare rebound tonometer and Perkins applanation tonometer (PAT) during community eye screening and to assess the agreement between these 2 instruments.
Design: A cross-sectional, non-interventional study.
Methods: The IOP measurements by handheld Icare rebound tonometer (Finland) were first performed by a primary care physician. Then the IOP was measured using Perkins Mk3 applanation tonometer (Haag-Streit, UK) by an ophthalmologist who was masked to previous readings from the Icare rebound tonometer. The mean IOP measured by each tonometer was compared. Pearson correlation coefficient was used to explore the correlation between the IOP measurements of the 2 instruments. The level of agreement between them was assessed using the Bland and Altman method.
Results: A total of 420 left eyes were examined. The mean age of subjects was 38.6 ± 18.2 years. Approximately 67% of subjects were female. The mean IOP was 16.3 ± 4.0 mm Hg using Icare and 13.4 ± 2.3 mm Hg using PAT. Pearson correlation coefficient showed a moderate positive correlation between the 2 methods (r = +0.524, P < 0.001). Linear regression analysis revealed a slope of 0.28 with R2 of 0.255. The mean difference between the 2 methods was 2.90 ± 3.5 mm Hg and the sample t-test revealed a statistically significant mean difference from 0 (P < 0.001). The 95% limits of agreement between the 2 methods were between −9.73 and 3.93 mm Hg.
Conclusions: The handheld Icare rebound tonometer is a reasonably acceptable screening tool in community practices. However, Icare overestimated IOP with a mean of 2.90 mm Hg higher than the PAT. Thus, using Goldmann applanation tonometer as a confirmatory measurement tool of IOP is suggested.
Delivery Characteristics of the Preloaded POB-MA 877PA Intraocular Lens System: Comparison of 2 Incision Sizes Yao, Anthony; Liu, Henry
Purpose: To obtain real-world data regarding the delivery characteristics of a preloaded delivery system, the Bi-Flex POB-MA 877PA, and to compare them in 2 main port incision sizes: 2.4 mm and 2.75 mm.
Design: Prospective multicenter observational cohort study.
Methods: Consecutive elective phacoemulsification and intraocular lens surgeries using the POB-MA 877PA implant were performed by a single experienced surgeon between December 2017 and April 2018. Patients were divided into 2 groups with group 1 and 2 underwent phacoemulsification through a main port size of 2.4 mm and 2.75 mm, respectively. Delivery characteristics were recorded, with a main outcome defined as lens delivery entirely into the capsular bag using the preloaded injector without additional manipulation. Other variances were classified as minor or major issues depending on lens or anatomical damage or requirement to replace device.
Results: A total of 110 total cases were included, with 59 cases in group 1 (2.4 mm) and 51 cases in group 2 (2.75 mm). Group 2 had a significantly lower proportion of cases that required secondary manipulation of the lens than group 1 [8 (15.7%) cases vs 24 (40.7%) cases; P < 0.05]. In groups 1 and 2, 3 (5.1%) and 3 (5.9%) cases had major issues, respectively.
Conclusions: The delivery characteristics of the POB-MA 877PA intraocular lens systems are different in the 2.4-mm and 2.75-mm main port incisions, with a lower proportion of cases requiring secondary manipulation in the 2.75-mm incision size. Despite its preloaded nature however, there are still delivery issues with these intraocular lens systems.

Review Article

Current Outcomes of Anti-VEGF Therapy in the Treatment of Macular Edema Secondary to Central Retinal Vein Occlusions: A Systematic Review and Meta-Analysis Spooner, Kimberly; Hong, Thomas; Fraser-Bell, Samantha; Chang, Andrew
Purpose: To evaluate the current anti–vascular endothelial growth factor (anti-VEGF) treatments for macular edema due to central retinal vein occlusions.
Methods: PubMed, EMBASE, the Cochrane Library were systematically searched for studies between January 2013 and July 2018. Reference lists of published articles were searched and if necessary, authors were contacted to provide additional data. Meta-analysis was performed using Comprehensive Meta-analysis software. The best-corrected visual acuity (BCVA), central foveal thickness (CFT), injection frequency, and adverse events were evaluated.
Results: Seventeen studies involving 1070 eyes were included in the meta-analysis. The mean differences in 12-month changes in BCVA and CFT were 14.4 ETDRS letters (P < 0.001) and −289.2 μm (P < 0.001), respectively. Visual acuity gains were maintained at 24 months (14.2 letters, P < 0.001) and CFT continued to reduce (−327.45 μm, P < 0.001). The incidence of severe adverse events was low and similar across all anti-VEGF therapies. Prospective studies administered a greater number of injections compared with retrospective studies, being 6.6 and 4.4 injections, respectively over 12 months (P < 0.001).
Conclusion: Intravitreal treatment with anti-VEGF agents demonstrated significant anatomical and functional gains in treating macular edema due to central retinal vein occlusions.
Optic Disc Pit Maculopathy: A Review Kalogeropoulos, Dimitrios; Ch’ng, Soon Wai; Lee, Rynn; Elaraoud, Ibrahim; Purohit, Maninee; Felicida, Vinaya; Mathew, Magie; Ajith-Kumar, Naduviledeth; Sharma, Ash; Mitra, Arijit
Optic disc pit (ODP) is a rare congenital anomaly of the optic disc that can be associated with maculopathy leading to progressive visual deterioration. The vast majority of cases are sporadic and no obvious factors have been correlated with the development of maculopathy. Optic disc pit maculopathy is defined by the concentration of intraretinal and subretinal fluid at the area of macula. Despite the advances in the imaging of the fundus, the origin of the fluid remains unknown and the exact pathogenesis of the maculopathy is not fully understood. Although some cases have been reported to resolve spontaneously, most cases require surgical intervention in order to treat ODP maculopathy and prevent loss of vision. Currently, there is no definite treatment for these patients and several surgical methods have been described, including pars plana vitrectomy (PPV) (combined with various techniques, such as inner retinal fenestration, autologous fibrin, and glial tissue removal), laser photocoagulation, intravitreal gas injection, and macular buckling. Overall, PPV remains the main form of surgical repair of ODP maculopathy. Although our understanding of the background and the pathophysiology of the disease has significantly improved, more studies are required in order to define the optimal treatment. This review summarizes the potential pathogenesis, as well as the diagnostic and therapeutic approach of ODP maculopathy.
How to Add Metacognition to Your Continuing Professional Development: Scoping Review and Recommendations Mack, Heather G.; Spivey, Bruce; Filipe, Helena P.
Participation in continuing professional development (CPD) is part of lifelong learning required by ophthalmologists. Metacognition is a new area of educational research. It is important because metacognitive skills are essential in medical education and likely to improve effectiveness of CPD activities. We systematically searched PubMed using the terms “metacognition” and “CPD” or “continuing medical education (CME)” and found only 5 articles. These articles were supplemented by a broadbased review of published literature including educational psychology, across the continuum of medical education. We summarize the techniques that may improve metacognition in CPD: awareness of and instruction in metacognition, awareness and mitigation of cognitive errors, appropriate needs analysis, and choosing appropriate activities. Metacognition and learning of new surgical techniques, the role of portfolios, and the role of the educator are described. The evidence is weak however, and it is usually extrapolated to CPD activities from other fields. Ophthalmologists may be able to improve their metacognitive skills in the CPD context, but the evidence supporting this is of low quality.
Promising Artificial Intelligence–Machine Learning–Deep Learning Algorithms in Ophthalmology Balyen, Lokman; Peto, Tunde
The lifestyle of modern society has changed significantly with the emergence of artificial intelligence (AI), machine learning (ML), and deep learning (DL) technologies in recent years. Artificial intelligence is a multidimensional technology with various components such as advanced algorithms, ML and DL. Together, AI, ML, and DL are expected to provide automated devices to ophthalmologists for early diagnosis and timely treatment of ocular disorders in the near future. In fact, AI, ML, and DL have been used in ophthalmic setting to validate the diagnosis of diseases, read images, perform corneal topographic mapping and intraocular lens calculations. Diabetic retinopathy (DR), age-related macular degeneration (AMD), and glaucoma are the 3 most common causes of irreversible blindness on a global scale. Ophthalmic imaging provides a way to diagnose and objectively detect the progression of a number of pathologies including DR, AMD, glaucoma, and other ophthalmic disorders. There are 2 methods of imaging used as diagnostic methods in ophthalmic practice: fundus digital photography and optical coherence tomography (OCT). Of note, OCT has become the most widely used imaging modality in ophthalmology settings in the developed world. Changes in population demographics and lifestyle, extension of average lifespan, and the changing pattern of chronic diseases such as obesity, diabetes, DR, AMD, and glaucoma create a rising demand for such images. Furthermore, the limitation of availability of retina specialists and trained human graders is a major problem in many countries. Consequently, given the current population growth trends, it is inevitable that analyzing such images is time-consuming, costly, and prone to human error. Therefore, the detection and treatment of DR, AMD, glaucoma, and other ophthalmic disorders through unmanned automated applications system in the near future will be inevitable. We provide an overview of the potential impact of the current AI, ML, and DL methods and their applications on the early detection and treatment of DR, AMD, glaucoma, and other ophthalmic diseases.
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