Clinical Correlation of Retinal Fluid Fluctuation Represented by Fluctuation Index in Wet Age-Related Macular Degeneration: TOWER Study Report 2.

Purpose: To explore outcomes and biomarkers associated with retinal fluid instability represented by a new parameter in neovascular age-related macular degeneration (nAMD). Methods: Patients with treatment-naïve nAMD receiving anti-vascular endothelial growth factor (VEGF) injections for a duration of 1 to 3 years were consecutively reviewed. Fluctuation Index (FI) of each eye, calculated by averaging the sum of differences in 1-mm central subfield thickness between each follow-up from months 3 to 24, was arranged into ascending order from the lowest to the highest and split equally into low, moderate, and high fluctuation groups. Outcomes were analyzed at 24 months. Results: Of 558 eyes, FI values showed a negative correlation with a degree-response gradient with 24-month visual improvement. After controlling for baseline best-corrected visual acuity and potential confounders, eyes with low fluctuation gained more Early Treatment Diabetic Retinopathy Study letters than those in the moderate and high fluctuation group (Δ, 10.1 and 14.0 letters, respectively). Significant best-corrected visual acuity improvement from baseline to month 24 (11.8 letters) was observed exclusively in the low fluctuation group despite the indifference in the number of injections and types of anti-VEGF drug used among groups. Patients presenting with central subfield thickness of ≥405 µm or intraretinal fluid coinciding with subretinal fluid showed a significant association with foveal thickness instability during the maintenance phase. Conclusions: Apart from the central subfield thickness values, unstable macular thickening represented by the FI was associated with some baseline features and may contribute to substandard visual outcomes. Translational Relevance: FI may be a valuable tool for assessing therapeutic adequacy in the treatment of nAMD.

Cost-Utility Analysis of Deep Learning and Trained Human Graders for Diabetic Retinopathy Screening in a Nationwide Program.

INTRODUCTION: Deep learning (DL) for screening diabetic retinopathy (DR) has the potential to address limited healthcare resources by enabling expanded access to healthcare. However, there is still limited health economic evaluation, particularly in low- and middle-income countries, on this subject to aid decision-making for DL adoption. METHODS: In the context of a middle-income country (MIC), using Thailand as a model, we constructed a decision tree-Markov hybrid model to estimate lifetime costs and outcomes of Thailand's national DR screening program via DL and trained human graders (HG). We calculated the incremental cost-effectiveness ratio (ICER) between the two strategies. Sensitivity analyses were performed to probe the influence of modeling parameters. RESULTS: From a societal perspective, screening with DL was associated with a reduction in costs of ~ US$ 2.70, similar quality-adjusted life-years (QALY) of + 0.0043, and an incremental net monetary benefit of ~ US$ 24.10 in the base case. In sensitivity analysis, DL remained cost-effective even with a price increase from US$ 1.00 to US$ 4.00 per patient at a Thai willingness-to-pay threshold of ~ US$ 4.997 per QALY gained. When further incorporating recent findings suggesting improved compliance to treatment referral with DL, our analysis models effectiveness benefits of ~ US$ 20 to US$ 50 depending on compliance. CONCLUSION: DR screening using DL in an MIC using Thailand as a model may result in societal cost-savings and similar health outcomes compared with HG. This study may provide an economic rationale to expand DL-based DR screening in MICs as an alternative solution for limited availability of skilled human resources for primary screening, particularly in MICs with similar prevalence of diabetes and low compliance to referrals for treatment.

Treatment Outcome of Wet Age-Related Macular Degeneration Management in Thailand: A Retrospective Real-World Study (TOWER Study).

INTRODUCTION: To present real-world outcomes of neovascular age-related macular degeneration (nAMD) management in Thailand. METHODS: This multicenter retrospective study reviewed medical records of naive nAMD patients diagnosed from 1 January 2016 until 31 December 2018. The patients received at least one intravitreal anti-vascular endothelial growth factor (VEGF) treatment and had captured visual acuity (VA) at baseline and at month 12. Treatment outcomes were assessed at month 12, 24, and 36. The primary outcome was a mean change in VA from baseline to month 12. RESULTS: Five hundred seventy-two (572) eyes were included in this study and of these eyes, 222 and 96 had 2- and 3-year follow-up periods, respectively. At month 12, the mean improvement of VA (ETDRS letter) was six letters (P < 0.0001), and central retinal thickness (CRT) decreased on average by 104 microns (P < 0.0001). However, visual improvement by 0.1 letters at month 36 did not show statistical significance. The presence of fluid was found in approximately half of patients throughout the study period (45.98%, 48.85%, and 50.91% at month 12, 24, and 36, respectively). Mean number of injections (SD) was 6.06 (3.00), 3.44 (2.94), and 2.71 (3.07) for years 1, 2, and 3, respectively. The mean number of visits (SD) in year 1 was 9.01 (2.60) and declined to 5.67 (2.69) in year 2 and 4.93 (2.49) in year 3. Patients who had an average injection interval of ≤ 8 weeks were 74.46% in year 1, 51.28% in year 2, and 45.24 in year 3; 35.31% of patients were lost to follow-up. CONCLUSIONS: This analysis reflects real-world nAMD management with significant improvement of outcomes. At the same time, the study reveals unmet needs in anti-VEGF therapy in nAMD including persistent disease activities, inadequacy of available treatment, and lack of treatment adherence leading to visual deterioration in the long-term.

Development of Diabetic retinopathy screening guidelines in South-East Asia region using the context, challenges, and future technology.

OBJECTIVE: To formulate guidelines for screening of diabetic retinopathy (DR) for the World Health Organization (WHO) South-East Asia Region (SEAR) aligned with the current infrastructure and human resources for health (HRH). DESIGN: A consultative group discussion of technical experts of the International Agency for the Prevention of Blindness (IAPB) from SEAR. PARTICIPANTS: IAPB country chairs and DR technical experts from SEAR countries. METHODS: Data related to DR in SEAR was collected from published literature on available DM and DR guidelines and the participating experts. The 10 SEAR countries (the Democratic Republic of Korea was not included for lack of sufficient data) were divided into 3 resource levels (low, medium, and high) based on gross national income/per capita, cataract service indicators (cataract surgical rate and cataract surgical service), current infrastructure and available HRH. Two countries each were assigned to low (Myanmar, Timor-Leste) and high resource (India, Thailand) levels, and the remaining 6 countries (Bangladesh, Bhutan, Indonesia, Maldives, Nepal, Sri Lanka) were assigned the medium resource level. The DR care system was divided into 3 levels of care (essential, recommended, and desirable) and 3 levels of service delivery (primary, secondary, and tertiary). MAIN OUTCOME MEASURES: Primary, secondary, and tertiary level guidelines for screening of DR. RESULTS: Nine WHO SEAR countries participated in the formulation of the new country-specific DR screening guidelines. The DR screening recommendations were: advocacy at the community level, visual acuity measurement, and non-mydriatic fundus photography at the primary level, comprehensive eye examination and retinal laser at the secondary level, and intravitreal therapy and vitrectomy at the tertiary level. The systemic care of DM and hypertension are recommended at all levels commiserating with their care capabilities. CONCLUSIONS: The DR guidelines for the SEAR region are the first region-specific and resource-aligned recommendations for comprehensive DR care in each country of the region. In the future, the new technological advances in retinal camera technology, teleophthalmology, and artificial intelligence should be included within the structure of the public DR care system.

A real-world study of effectiveness of intravitreal bevacizumab and ranibizumab injection for treating retinal diseases in Thailand.

BACKGROUND: To evaluate the effectiveness of intravitreal bevacizumab (IVB) and intravitreal ranibizumab (IVR) in actual practice for treating patients with retinal diseases in Thailand. METHODS: A prospective, multi-centre, observational study was conducted among eight hospitals in their ophthalmology outpatient departments. Participants consisted of patients who had previously not received any IVB or IVR treatment between 2013 and 2014. The primary outcome measurement was the change in best-corrected visual acuity (BCVA) at the end of the follow-up period compared to baseline. RESULTS: There were 1629 treatment-naïve patients for the pro re nata (PRN) treatment pattern and 226 treatment-naive patients for the three-injections (3Inj) treatment pattern. BCVA improvements were found in 35% of the PRN group and 47% of the 3Inj group; however, it was not clinically meaningful between the IVB and IVR groups (P-value = 0.568 for PRN, P-value = 0.103 for 3Inj). A multivariable logistic regression (using the propensity score) showed that positive factors associated with vision improvement for the PRN pattern were the number of drug injections, having retinal vein occlusion, and under 60 years of age, while good BCVA at baseline was a negative predictive factor. For the 3Inj pattern, under 60 years of age and baseline BCVA were statistically significant predictors. Nonetheless, diabetes mellitus (DM) without other comorbidities was a statistically significant predictor of low response to vision improvement compared to DM with other comorbidities. CONCLUSIONS: This study was the first observational, prospective study to evaluate the real-life effectiveness of IVB and IVR in Thailand. The majority of participants who used IVB or IVR showed improvements in BCVA after treatment. Further evaluation such as long-term follow-ups and subsequent comparison of effectiveness between IVB and IVR should be investigated due to the limited sample of IVR patients. TRIAL REGISTRATION: Thai Clinical Trial Registry TCTR20141002001 . Registered 02 October 2014 (retrospectively registered).

Correction to: Real-World Safety of Intravitreal Bevacizumab and Ranibizumab Treatments for Retinal Diseases in Thailand: A Prospective Observational Study.

The Open Access license, which previously read.

Real-World Safety of Intravitreal Bevacizumab and Ranibizumab Treatments for Retinal Diseases in Thailand: A Prospective Observational Study.

BACKGROUND: There is very limited evidence examining serious systemic adverse events (SSAEs) and post-injection endophthalmitis of intravitreal bevacizumab (IVB) and intravitreal ranibizumab (IVR) treatments in Thailand and low- and middle-income countries. Moreover, findings from the existing trials might have limited generalizability to certain populations and rare SSAEs. OBJECTIVES: This prospective observational study aimed to assess and compare the safety profiles of IVB and IVR in patients with retinal diseases in Thailand. METHODS: Between 2013 and 2015, 6354 patients eligible for IVB or IVR were recruited from eight hospitals. Main outcomes measures were prevalence and risk of SSAEs, mortality, and endophthalmitis during the 6-month follow-up period. RESULTS: In the IVB and IVR groups, 94 and 6% of patients participated, respectively. The rates of outcomes in the IVB group were slightly greater than in the IVR group. All-cause mortality rates in the IVB and IVR groups were 1.10 and 0.53%, respectively. Prevalence rates of endophthalmitis and non-fatal strokes in the IVB group were 0.04% of 16,421 injections and 0.27% of 5975 patients, respectively, whereas none of these events were identified in the IVR group. There were no differences between the two groups in the risks of mortality, arteriothrombotic events (ATE), and non-fatal heart failure (HF). Adjustment for potential confounding factors and selection bias using multivariable models for time-to-event outcomes and propensity scores did not alter the results. CONCLUSIONS: The rates of SAEs in both groups were low. The IVB and IVR treatments were not associated with significant risks of mortality, ATE, and non-fatal HF. TRIAL REGISTRATION: Thai Clinical Trial Registry identifier TCTR20141002001.

Is the 2015 eye care service delivery profile in Southeast Asia closer to universal eye health need!

PURPOSE: The year 2015 status of eye care service profile in Southeast Asia countries was compared with year 2010 data to determine the state of preparedness to achieve the World Health Organization global action plan 2019. METHODS: Information was collected from the International Agency for Prevention of Blindness country chairs and from the recent PubMed referenced articles. The data included the following: blindness and low vision prevalence, national eye health policy, eye health expenses, presence of international non-governmental organizations, density of eye health personnel, and the cataract surgical rate and coverage. The last two key parameters were compared with year 2010 data. RESULTS: Ten of 11 country chairs shared the information, and 28 PubMed referenced publications were assessed. The prevalence of blindness was lowest in Bhutan and highest in Timor-Leste. Cataract surgical rate was high in India and Sri Lanka. Cataract surgical coverage was high in Thailand and Sri Lanka. Despite increase in number of ophthalmologists in all countries (except Timor-Leste), the ratio of the population was adequate (1:100,000) only in 4 of 10 countries (Bhutan, India, Maldives and Thailand), but this did not benefit much due to unequal urban-rural divide. CONCLUSION: The midterm assessment suggests that all countries must design the current programs to effectively address both current and emerging causes of blindness. Capacity building and proportionate distribution of human resources for adequate rural reach along with poverty alleviation could be the keys to achieve the universal eye health by 2019.

Epidemiology of Age-Related Macular Degeneration among the Elderly Population in Thailand.

OBJECTIVE: To estimate the prevalence and associated factors of age-related macular degeneration (AMD) in Thailand. MATERIAL AND METHOD: This cross-sectional survey was undertaken in 2010. Five provinces were selected and people aged 50 years and over were invited for eye examination. Demographic and health behaviors and data from eye examination equipment were registered. Ophthalmologists graded AMD as early or late based on fundus color photograph and image from optical coherence tomography. Logistic regressions were analyzed to establish associationfactorsfor AMD. RESULTS: Of the 7,043 participants, AMD wasfound in 862 people (12.2%), with more than half (53.1%) found in both eyes. Most cases (94.3%) were early dry, 1.8% early wet, 3.4% late dry, and 0.7% late wet AMD. Factors positively associated with AMD were age (OR 1.03, 95% CI 1.02-1.04), diabetes mellitus (OR 1.20, 95% CI 1.03-1.39), and consumption of yellow vegetable (OR 2.32, 95% CI 1.23-4.39). Factors that conversely associated with AMD were consumption of green vegetable (OR 0.51, 95% CI 0.33-0.79), physical exercise (OR 0.67, 95% CI 0.51-0.87), high bloodpressure (OR 0.75,95% CI 0.63-0.89), and heavy drinking habit (OR 0.45, 95% CI 0.26-0.75). CONCLUSION: The prevalence of AMD in Thai population age 50 and over was 12.2%. More than half (53.1%) of the cases were found in both eyes, but few at severe stages. The present study confirmed age and DM as positive associated factors, and green vegetable, exercise as negative associated factors. Further research should investigate the effects of hypertension, yellow vegetable, and alcohol drinking on AMD.

Randomized controlled trial of subconjunctival bevacizumab injection in impending recurrent pterygium: a pilot study.

PURPOSE: To investigate the efficacy and safety of subconjunctival bevacizumab injection for the treatment of impending recurrent pterygium. METHODS: A prospective, randomized, single-masked, controlled trial was conducted in 80 patients with impending recurrent pterygium. Patients were randomized into 4 groups using random tables: 20 patients served as a control and treatment groups received a single intralesional injection of 1.25 mg (20 patients, group 1), 2.5 mg (20 patients, group 2), or 3.75 mg (20 patients, group 3) of bevacizumab. Topical 0.1% fluorometholone and ocular lubricant were administered 4 times daily for 1 month in all groups. Severity of impending recurrent pterygium graded by photographic assessment (at baseline, 3 days, 1 week, and 2, 4, 8, and 12 weeks after treatment) and true recurrence were the main outcome measures. RESULTS: At 3 days, the conjunctival injection significantly decreased in all treatment groups (P < 0.01). A significant decrease in the conjunctival injection was still observed until 2 and 4 weeks in only groups 2 and 3, respectively (P < 0.05). The conjunctival hyperemia appeared to increase back to baseline at later time points. No significant difference in the mean severity score among the groups was observed. True recurrence was found in 62 patients with no statistically significant difference among the groups. No serious ocular or systemic adverse events were seen. CONCLUSIONS: A single subconjunctival bevacizumab injection seems to only partially and transiently decrease conjunctival vascularization in impending recurrent pterygium in a dose-dependent manner. This treatment does not cause regression or reduce the recurrent rate of impending recurrent pterygium.

Photodynamic therapy for AMD and non-AMD patients: one-year results in Thais.

OBJECTIVE: To evaluate the effect of photodynamic therapy (PDT) with verteporfin for age-related macular degeneration (AMD) and non-AMD in Thais, and compare with the Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) and Verteporfin in Photodynamic Therapy (VIP) study. MATERIAL AND METHOD: The authors prospectively evaluated all data of 51 eyes of 51 patients who had undergone PDT and accomplished a 1-year follow up. The assessments were divided into two categories: group 1 included three subsets of AMD, and group 2 was non-AMD. The first group classified into three subgroups: group 1A: AMD with subfoveal choroidal neovascularization (CNV) and TAP/VIP compatible with recommendation guidelines characteristics, group 1B: AMD with subfoveal CNV and TAP/VIP incompatible, and group 1C: AMD with non-subfoveal CNV. The measurement outcomes comprised of the baseline characteristics, change in visual acuity, and number of treatments. RESULTS: Thirty-eight eyes had CNV-related AMD and 13 eyes were non-AMD. At the 12-month examination, the mean visual acuity change in group 1A, 1B, 1C had increased 0.19 (p = 0.077), 0.14 (p = 0.076), and 0.24 (p = 0.003), respectively. The number of treatments was 1.8 in group 1A, 2.3 in group 1B, and 1.5 in group 1C. CONCLUSION: PDT is beneficial to Thai patients with AMD at first year even if they were not compatible with TAP/VIP criteria.