The Asia-Pacific Journal of Ophthalmology


An Update on Intravitreal Aflibercept in Treating Macular Diseases Lai, Timothy Y.Y.
Over the past decade, intravitreal anti‒vascular endothelial growth factor (anti-VEGF) agents have become the standard-of-care treatment of various macular diseases including neovascular age-related macular degeneration (AMD), diabetic macular edema (DME), macular edema due to retinal vein occlusion, and choroidal neovascularization (CNV) secondary to pathologic myopia. Currently, 3 anti-VEGF agents are commonly used for the treatment of macular diseases and they include ranibizumab (Lucentis; Novartis, Basel, Switzerland), aflibercept (Eylea; Bayer, Leverkusen, Germany), and off-label use of bevacizumab (Avastin; Roche, Basel, Switzerland). Among the 3 agents, aflibercept is the latest agent introduced into the market and was approved for the treatment of neovascular AMD by the US Food and Drug Administration in 2011. Since then, additional indications in the use of aflibercept have been obtained including DME, macular edema due to retinal vein occlusion, and myopic CNV. Aflibercept is unique among the 3 anti-VEGF agents as it also inhibits placental growth factor (PlGF). Experimental studies have also demonstrated that aflibercept has a higher blinding affinity for VEGF molecules compared with bevacizumab and ranibizumab. Therefore, with the additional property of PlGF inhibition and higher affinity for VEGF, aflibercept might theoretically have a longer duration of action compared with bevacizumab and ranibizumab.

Original Study - Clinical

Corneal Collagen Crosslinking for Post-LASIK Ectasia: An Australian Study Tong, Jessica Y.; Viswanathan, Deepa; Hodge, Christopher Hodge; Sutton, Gerard; Chan, Colin; Males, John J.
Purpose: Post laser-assisted in situ keratomileusis (LASIK) ectasia is a rare and unpredictable complication after LASIK. Corneal collagen crosslinking (CXL) has emerged as a promising technique to address this complication. Our study evaluates the long-term efficacy of CXL for post-LASIK ectasia in an Australian setting.

Design: Retrospective review of post-LASIK ectasia patients referred to and treated at 3 corneal refractive surgery institutions in Sydney, Australia.

Methods: Eleven patients (14 eyes; mean age, 39.7 ± 12.6 years) underwent epithelium-off CXL with follow-up ranging from 12‒78 months. Best spectacle-corrected visual acuity (BSC VA), simulated keratometry, corneal topography indices, and higher-order aberrations (HOA s) [mean ± standard error of the mean (SEM)] were measured with a rotating Scheimpflug camera (Pentacam, Oculus). Comparisons between baseline measurements and postoperative outcomes were performed using paired t test analysis.

Results: At last follow-up, BSCSCVA improved significantly by 0.2 ± 0.06 logMARAR (P = 0.01), and 12 of 14 eyes showed no keratometric deterioration. Of the corneal topography indices, index of height asymmetry showed a trend toward a significant improvement (P = 0.05). There was no progression of corneal HOAOAs. Central corneal thickness was not significantly altered (P = 0.6). No major postoperative complications were observed.

Conclusions: In the Australian setting, CXL has proven effective at stabilizing the progression of post-LASIK ectasia, inducing corneal regularity, and improving visual acuity.
Cap Lenticular Adhesion During Small Incision Lenticular Extraction Surgery: Causative Factors and Outcomes Shetty, Rohit; Negalur, Nikhil; Shroff, Rushad; Deshpande, Kalyani; Jayadev, Chaitra
Purpose: To study the factors causing cap lenticular adhesion (CLA), a rare complication of small incision lenticule extraction (SMILE) surgery, and its effect on surgical outcomes.

Design: A prospective, observational, cross-sectional study involving 550 eyes of 285 subjects.

Methods: SMILE was performed using the VisuMax femtosecond laser (Carl Zeiss Meditec, Jena, Germany) with a minimum of 3 months follow-up. Preoperative visual quality assessment, measurement of corneal biomechanics, and Bowman membrane imaging were performed. Based on the mean refractive spherical equivalent (MRSE), subjects were classified into mild, moderate, and high myopes. Causes of CLA and postoperative outcomes were evaluated.

Results: CLA was seen in 1.8% of patients, in whom the median preoperative MRSE was −1.5 (−2.75 to −1.38), deformation amplitude was 1.13 (1.10 to 1.21), and lenticular thickness was 46.2 (39.9 to 54.31). They had microdistortions in the Bowman layer and poor quality of vision. A median Strehl ratio of 0.08 (0.07 to 0.11) and modulation transfer function of 9.88 (8.98 to 13.34) were noted on the first day after surgery, which gradually improved to 0.17 (0.15 to 0.18) and 33.90 (27.27 to 38.94), respectively. On observing the surgical videos, a distinct shining reflection, “the shimmer sign,” was seen around the dissector in patients with CLA when the posterior plane was dissected before the anterior.

Conclusions: Cap lenticular adhesion was associated with a low preoperative MRSE and thin lenticules. The shimmer sign serves as an indicator for identification of the correct plane of dissection.
Factors Related to Prostaglandin-Associated Periorbitopathy in Glaucoma Patients Patradul, Chanikarn; Tantisevi, Visanee; Manassakorn, Anita
Purpose: To determine factors related to prostaglandin-associated periorbitopathy (PAP) and its prevalence in glaucoma or ocular hypertension (OHT) patients using prostaglandins analogs (PGAs).

Design: A cross-sectional study.

Methods: A study of glaucoma or OHT patients, using topical PGAs for at least 3 months, was performed. Eyes treated with PGAs were photographed and independently evaluated for PAP by 2 glaucoma specialists using at least 4 out of 7 clinical appearances. The factors of interest were sex, age, body mass index (BMI), types of glaucoma, types of PGAs, duration of PGA use, and concurrent 0.5% timolol. Univariate (Χ2 test) and multivariate (multiple logistic regression) analyses assessing risk factors for PAP were performed to estimate the odds ratios (OR) with 95% confidence intervals.

Results: One hundred thirty-four eyes from 134 patients were included. Seventy (52.2%), 21 (15.7%), and 43 (32%) eyes received components of latanoprost, travoprost, and bimatoprost, respectively. Prevalence of PAP was 44.8% (95% CI, 36.3 to 53.3). Older age >60 years (OR, 3.0; 95% CI, 1.2 to 7.8), bimatoprost (OR, 4.0; 95% CI, 1.6 to 9.5), travoprost (OR, 3.3; 95% CI, 1.1 to 10.1), and timolol (OR, 2.9; 95% CI, 1.3 to 6.8) were at risk of PAP development. In addition, BMI ≥ 23 kg/m2 (OR, 0.3; 95% CI, 0.1 to 0.7) was reversely associated with PAP.

Conclusions: Older age, bimatoprost, or travoprost were associated with PAP, whereas high BMI was found as a protective factor. Interestingly, timolol possibly precipitated periorbital change when in use with prostaglandins.
Awareness and Knowledge of Glaucoma in Central India: A Hospital-Based Study Maharana, Prafulla K.; Rai, Vaishali G. Rai, Pattebahadur, Rajesh; Singhi, Shipra; Chauhan, Ashish K.
Purpose: To assess the awareness and knowledge of glaucoma among people attending the ophthalmology outpatient department at a tertiary care hospital in central India.

Design: A prospective observational study.

Methods: A questionnaire-based study was conducted, involving persons aged 18 and above attending the ophthalmology outpatient department from October 2014 to September 2015. Data on awareness and knowledge of glaucoma was collected through a face-to-face interview.

Results: Fourteen hundred people participated in the study. The mean age of participants was 43 ± 15 years (range, 18–85). The study participants included 53% men and 47% women. Only 27% (n = 380/1400) of the participants were aware of glaucoma. Age, sex, and presence or type of refractive error had no impact on glaucoma awareness. Awareness level was greater in individuals with higher education levels and those belonging to an upper socioeconomic class (SEC). Multiple logistic regression analysis revealed significantly higher levels of glaucoma awareness among participants belonging to the upper 2 SECs (P = 0.05) and those educated above the high school level (P = 0.001). The most common source of awareness was close acquaintance with relatives, family members, and friends of glaucoma patients.

Conclusions: Awareness of glaucoma in India is low. Lack of education and lower socioeconomic status are the major risk factors for late presentation of glaucoma. Continuous presence of a low level of awareness and the same factors accounting for it warrants the need for an aggressive and refined approach to increase awareness of glaucoma to prevent glaucoma-related blindness.
Intravitreal Aflibercept for Patients With Diabetic Macular Edema Refractory to Bevacizumab or Ranibizumab: Analysis of Response to Aflibercept Chen, Yen-Yi; Chang, Pei-Yao; Wang, Jia-Kang
Purpose: To investigate the short-term efficacy and safety of intravitreal aflibercept in a case series of patients with diabetic macular edema (DME) refractory to ranibizumab or bevacizumab.

Design: A retrospective chart review.

Methods: From September 2013 to March 2016, we identified patients with DME who developed resistance to bevacizumab or ranibizumab. Three monthly intravitreal aflibercept injections were administered in refractory cases. Nonresponse to aflibercept was defined as a paradoxical increase in central foveal thickness (CFT) and gain in best-corrected visual acuity (BCVA) of less than 1 line at 1 month after treatment compared with before aflibercept administration.

Results: Out of a total of 72 eyes in 72 refractory patients, 42 eyes (58.3%) responded to aflibercept injections. The BCVA and CFT were 0.65 ± 0.32 logMAR and 438.5 ± 80.1 μm, respectively, before aflibercept treatment and significantly improved to 0.31 ± 0.17 logMAR (P = 0.0008) and 297.9 ± 19.1 μm (P = 0.0004), respectively, 1 month after 3 aflibercept injections in responders. No differences in baseline characteristics, including age, sex, glycosylated hemoglobin, serum creatinine, total cholesterol, lens status, grades of diabetic retinopathy, and CFT/BCVA before aflibercept management (P > 0.05), were observed between responders and nonresponders. There were 17 vitrectomized eyes in 30 nonresponders (56.7%), a significantly higher rate than among the 42 responders (0%; P = 0.00001). Conclusions: Three monthly intravitreal aflibercept injections had benefit in nearly two thirds of cases with DME resistant to bevacizumab or ranibizumab over short-term follow-up. Vitrectomized eyes responded poorly to aflibercept treatment.

Posterior Pole and Peripheral Retinal Fibrovascular Proliferation in von Hippel Lindau Disease Elborgy, Ebrahim; Pulido, Jose S.
Purpose: To report the occurrence of fibrovascular proliferation (FVP) in the retina in von Hippel-Lindau (VHL) patients and its association with prior treatment.

Design: A retrospective study.

Methods: A retrospective study of 101 VHL patients. Fundus photos were available for 28 patients. FVP was classified into peripheral and posterior pole.

Results: All 28 patients had retinal capillary hemangioblastomas (RCH) in 1 or both eyes; 15 patients were found to have FVP (group A), whereas 13 patients did not (group B). Mean age of patients in group A was 35 ±11.3 years and 36.6 ± 13.8 in group B (P = 0.74). In group A, 27 eyes had RCH; 21 (77.77%) had FVP. In group B, 19 eyes had RCH. The number of treated eyes was significantly higher in group A (81.48%) than group B (42.1%) (P = 0.007). In group A, FVP was noted in the posterior pole in 9 eyes, in the periphery in 5 eyes, and 7 eyes developed both posterior pole and peripheral FVP.

Conclusions: FVP can occur in the peripheral retina and in the posterior pole. There is a significant association between prior treatment of RCH and the occurrence of FVP.
Quantitative Reduction in Central Foveal Thickness After First Anti-VEGF Injection as a Predictor of Final Outcome in BRVO Patients Roy, Rupak; Saurabh, Kumar; Ghose, Avirupa; Chandrasekharan, Dhileesh P.; Sharma, Preeti; Pal, Swakshyar Saumya; Das, Sudipta
Purpose: To analyze the predictive ability of quantitative reduction in central foveal thickness (CFT) after the first antivascular endothelial growth factor (anti-VEGF) injection to assess final outcome in branch retinal vein occlusion (BRVO) patients.

Design: A retrospective interventional consecutive case series.

Methods: We retrospectively reviewed 60 treatment-naive BRVO patients. All the patients were treated with bevacizumab injection pro re nata. We measured the reduction in CFT 1 month after injection and at each visit along with other optical coherence tomography (OCT) features like external limiting membrane (ELM) integrity, ellipsoid zone (EZ) integrity, and foveal bulge (FB).

Results: At final follow-up more patients in the >25% CFT reduction group had a better mean best-corrected visual acuity (BCVA) and dry macula as compared with the ≤25% group (0.25 logMAR vs 0.46 logMAR, P = 0.03; 28 eyes vs 9 eyes, P = 0.005). Based on the final visual outcome we divided patients into 2 groups: group 1, BCVA ≥ 20/40; group 2, BCVA < 20/40. Analysis at 1 month after injection revealed the ELM was intact in 27 (73%) and 5 (21.7%), EZ was intact in 28 (75.7%) and 11 (47.8%), and FB was intact in 12 (32.4%) and 2 (8.7%) patients, respectively, in groups 1 and 2 (P = 0.001, 0.02, 0.03).

Conclusions: Patients who have more than a 25% reduction 1 month after the first anti-VEGF injection and a restored ELM, EZ, and FB have a significantly higher likelihood of achieving BCVA ≥ 20/40.
Barriers to the Uptake of Cataract Surgery and Eye Care After Community Outreach Screening in Takeo Province, Cambodia Ormsby, Gail M.; Mörchen, Manfred; Fotis, Kathy; Skiba, Dawn Grant; Chim, Channeang; Keeffe, Jill E.
Purpose: To assess the barriers influencing eye healthcare seeking behavior after community outreach screening.

Design: A concurrent mixed methods study.

Methods: A total of 469 patients screened during the previous 12 months were followed up, of which 354 (75%) from 5 districts were interviewed in person, using a semi-structured questionnaire, in-depth interviews (n = 11), and 16 focus groups (n = 71). SPSS and NVivo were used to analyze response frequency and identify themes.

Results: Of the respondents, 98% (350/354) reported they were told they had an eye problem, with 295 individuals (83%) told to attend CARITAS Takeo Eye Hospital (CTEH) and 55 to have their eyes checked at Kiri Vong Vision Centre. Of those 68.9% (244/354) who reported seeking treatment, only 7.4% (18/244) reported they attended CTEH, 54% (n = 132) attended a “local pharmacy,” 31.6% (n = 77) “self-treated at home,” 11% (n = 27) reported “using steam from boiling rice,” and 10.7% (n = 26) attended a “traditional healer.” Of those who reported reasons for “not attending,” responses included “no time” (47.8%, 86/180), “no one to accompany” (21.7%, n = 39), “fear of losing sight” (17.8%, n = 32), “cannot afford to travel” (16.1%, n = 29), and “eye problem is not serious enough” (15.6%, n = 28). Follow-up of patient records identified that 128 individuals (79 females) attended eye care services.

Conclusions: Socioeconomic factors, personal concerns, and the use of local cultural remedies were reasons for not seeking eye hospital treatment. An integrated community approach to improve awareness and uptake of appropriate treatment is recommended.meaningful safety concerns.

Review Article

Neural Tumors of the Orbit—What Is New? Ghassibi, Mark P.; Ulloa-Padilla, Jan P.; Dubovy, Sander R.
Primary neural tumors of the orbit account for approximately 10% of all orbital tumors. Different tumor entities include meningiomas, optic nerve gliomas, neurofibromas, schwannomas, malignant peripheral nerve sheath tumors, and granular cell tumors. This review summarizes current concepts regarding epidemiology, clinical presentation, diagnosis, pathology, immunohistochemistry, prognosis, and treatment for neural tumors of the orbit based on the available literature.
Primary Vitreoretinal Lymphoma—A Review Araujo, Iguaracyra; Coupland, Sarah E.
Primary vitreoretinal lymphoma (PVRL) is the most common intraocular lymphoma occurring in the eye. It is a high-grade typically B-cell malignancy, arising in the retina, and is often associated with central nervous system (CNS) disease and thereby a poor prognosis. It needs to be distinguished from choroidal low-grade B-cell lymphomas, which do not disseminate to the brain and have a good prognosis. Because of the rarity of PVRL, information is lacking regarding its true incidence, its geographical or ethnic variation, and underlying risk factors apart from immunosuppression associated with human immunodeficiency virus (HIV) and Epstein Barr virus. PVRL often presents masquerading as other intraocular diseases and is therefore often associated with diagnostic delays. This is compounded by the fragility of the neoplastic B cells, which hampers vitrectomy yields and pathological work-up. The latter includes cytomorphology and immunoprofiling, with adjunctive tests such as cytokine analysis, polymerase chain reaction for clonality, MYD88 mutational testing, and possibly bespoke next generation sequencing. Recent examinations of PVRL and CNSL using whole genome sequencing confirm that these tumors arise from activated postgerminal center cells, reflecting their aggressive course in most cases. The treatment of PVRL varies between centers and is dependent on presence or absence of concomitant CNS disease. The prognosis remains poor, and yet progress is steadily being made through international collaborative clinical trials.
Retinoblastoma: Update on Current Management Cassoux, Nathalie; Lumbroso, Livia; Levy-Gabriel, Christine; Aerts, Isabelle; Doz, François; Desjardins, Laurence
Retinoblastoma is a rare cancer in children, where in less than a century of dire mortality there has been a cure in industrialized countries. Unfortunately, mortality remains high in emerging countries. The evolution of treatment makes it possible to go further by preserving

the eyeball but this must not be done at the cost of the reappearance of metastases. Herein we outline the evolution of treatment from the beginning of the 20th century until the last recent evolutions, trying to imagine what could be the future treatments. In this pathology, the ophthalmologist is a doctor who must cure his patient and enucleation is considered a

failure. This situation should not lead to shizophrenic situations where to keep an eye one would take risks with the life of the child. New international classifications, international prospective multicentric studies, and the search for blood biomarkers that can predict the risk of micrometastases could allow for better stratification of patients.
Recommended Guidelines for Use of Intravitreal Aflibercept With a Treat-and-Extend Regimen for the Management of Neovascular Age-Related Macular Degeneration in the Asia-Pacific Region: Report From a Consensus Panel Koh, Adrian; Lanzetta, Paolo; Lee, Won Ki; Lai, Chi-Chun; Chan, Wai-Man; Yang, Chung-May; Cheung, Chui Ming Gemmy
Purpose: To summarize recommendations for the use of intravitreal aflibercept with a treat-and-extend regimen to manage neovascular age-related macular degeneration (nAMD) in the Asia-Pacific region. Although anti–vascular endothelial growth factor therapies have improved the quality of life of patients with nAMD, a leading cause of blindness and visual impairment, the high treatment frequency recommended by current guidelines places a significant burden on patients and healthcare providers.

Design: Recommended guidelines from a consensus panel.

Methods: An expert panel formed a consensus on recommendations for use of intravitreal aflibercept as treatment of nAMD in the Asia-Pacific region.

Results: After 3 initial monthly doses, treatment interval could be extended by 4-week increments, to a maximum of 12 weeks, in patients with inactive disease. Conversely, in active disease, treatment intervals should be shortened, by 4 weeks, or to 4 weeks in cases of severe recurrence. Treatment could be ceased in patients with stable disease activity after 12 months of treatment at 12-week intervals, as a means to prevent over treatment and lifelong injections.

Conclusions: These recommendations could potentially minimize the number of treatments while maintaining efficacy and improve compliance by reducing the number of clinic visits compared with existing recommendations.

Letters to the Editor

Is Floaterectomy Worth the Risks? Tripathy, Koushik
To the Editor:

I read with interest the article reporting encouraging results after 2-port vitrectomy for floaters.1 I want to humbly discuss a few facts.
Floaterectomy—Risks, Safety, and Future Radke, Nishant; Lam; Dennis S.C.
We thank Dr. Tripathy for his interest in our article and appreciate the concerns

raised. We do not have data on the percentage and type of posterior vitreous detachment

(PVD) in these patients, but this suggestion is indeed an interesting one to be incorporated in further studies


In Dogrusöz M, Jager MJ, Damato B. Uveal Melanoma Treatment and Prognostication. Asia-Pac J Ophthalmol. 2017;6:186–196, the authors stated that “class 1 tumors are now subcategorized into class 1A and class 1B based on the differential expression of a marker, PRAME.”

It would be more accurate to state that “class 1 tumors can be subcategorized into class 1A and class 1B. Increased mortality within the patient group with class 1 tumors is associated with differential expression of a marker, PRAME, within the tumor.”
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