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 Table of Contents  
Year : 2020  |  Volume : 58  |  Issue : 2  |  Page : 131-133

Journal review

Department of Ophthalmology, RIO-GOH, Chennai, Tamil Nadu, India

Date of Submission02-Mar-2020
Date of Acceptance03-Apr-2020
Date of Web Publication17-Jun-2020

Correspondence Address:
Dr. Jiz Mary Santhosh
Sri Ramachandra University Campus, Porur, Chennai - 600 116, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/tjosr.tjosr_14_20

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How to cite this article:
Santhosh JM. Journal review. TNOA J Ophthalmic Sci Res 2020;58:131-3

How to cite this URL:
Santhosh JM. Journal review. TNOA J Ophthalmic Sci Res [serial online] 2020 [cited 2020 Jul 13];58:131-3. Available from: http://www.tnoajosr.com/text.asp?2020/58/2/131/286932

  Low-Concentration Atropine for Myopia Progression Study: a Randomized, Double-Blinded, Placebo-Controlled Trial of 0.05%, 0.025%, and 0.01% Atropine Eye Drops in Myopia Control Top

Yam JC, Jiang Y, Tang SM, Law AKP, Chan JJ, Wong E, et al. Low-concentration atropine for myopia progression (LAMP) study: A randomized, double-blinded, placebo-controlled trial of 0.05%, 0.025%, and 0.01% atropine eye drops in myopia control. Ophthalmol 2019;126:113-24.

Purpose:Low-concentration atropine is an emerging therapy for myopia progression, but its efficacy and optimal concentration remain uncertain. Our study aimed to evaluate the efficacy and safety of low-concentration atropine eye drops at 0.05%, 0.025%, and 0.01% compared with placebo over a 1-year period. Design: This was a randomized, placebo-controlled, double-masked trial. Participants: A total of 438 children aged 4–12 years with myopia of at least −1.0 diopter (D) and astigmatism of −2.5 D or less were included in the study. Methods: Participants were randomly assigned in a 1:1:1:1 ratio to receive 0.05%, 0.025%, and 0.01% atropine eye drops or placebo eye drop, respectively, once nightly to both eyes for 1 year. Cycloplegic refraction, axial length (AL), accommodation amplitude, pupil diameter, and best-corrected visual acuity were measured at baseline, 2 weeks, 4 months, 8 months, and 12 months. The Visual Function Questionnaire was administered at the 1-year visit. Main Outcome Measures: Changes in spherical equivalent (SE) and AL were measured, and their differences among groups were compared using a generalized estimating equation. Results: After 1 year, the mean SE change was −0.27 ± 0.61 D, −0.46 ± 0.45 D, −0.59 ± 0.61 D, and −0.81 ± 0.53 D in the 0.05%, 0.025%, and 0.01% atropine groups and placebo group, respectively (P < 0.001), with a respective mean increase in AL of 0.20 ± 0.25 mm, 0.29 ± 0.20 mm, 0.36 ± 0.29 mm, and 0.41 ± 0.22 mm (P < 0.001). The accommodation amplitude was reduced by 1.98 ± 2.82 D, 1.61 ± 2.61 D, 0.26 ± 3.04 D, and 0.32 ± 2.91 D, respectively (P < 0.001). The pupil sizes under photopic and mesopic conditions were increased respectively by 1.03 ± 1.02 mm and 0.58 ± 0.63 mm in the 0.05% atropine group, 0.76 ± 0.90 mm and 0.43 ± 0.61 mm in the 0.025% atropine group, 0.49 ± 0.80 mm and 0.23 ± 0.46 mm in the 0.01% atropine group, and 0.13 ± 1.07 mm and 0.02 ± 0.55 mm in the placebo group (P < 0.001). Visual acuity and vision-related quality of life were not affected in each group.

Take-home message

This randomized control trial evaluated various dilutions of atropine eye drops (0.05%, 0.025%, and 0.01%) for controlling myopic SE progression and AL elongation in children over a 1-year period in comparison to placebo. The study revealed that low-concentration atropine was effective in limiting progression in myopic parameters, with 0.05% atropine being most effective. All concentrations showed good tolerability without affecting the vision-related quality of life.

  Hawk and Harrier: Phase 3, Multicenter, Randomized, Double-Masked Trials of Brolucizumab for Neovascular Age-Related Macular Degeneration Top

Dugel PU, Koh A, Ogura Y, Jaffe GJ, Schmidt-Erfurth U, Brown DM, et al. HAWK and HARRIER: Phase 3, multicenter, randomized, double-masked trials of brolucizumab for neovascular age-related macular degeneration. Ophthalmol 2020;127:72-84.

Purpose: Two similarly designed Phase 3 trials (HAWK and HARRIER) compared brolucizumab, a single-chain antibody fragment that inhibits vascular endothelial growth factor-A, with aflibercept to treat neovascular age-related macular degeneration (AMD). Design: These were double-masked, multicenter, active-controlled, randomized trials. Participants: Patients (n = 1817) with untreated, active choroidal neovascularization due to AMD in the study eye were included in the study. Intervention: Patients were randomized to intravitreal brolucizumab 3 mg (HAWK only) or 6 mg or aflibercept 2 mg. After loading with 3 monthly injections, brolucizumab-treated eyes received an injection every 12 weeks (q12w) and were interval adjusted to every 8 weeks (q8w) if disease activity was present; aflibercept-treated eyes received q8w dosing. Main Outcome Measures: The primary hypothesis was noninferiority in mean best-corrected visual acuity (BCVA) change from baseline to week 48 (margin: 4 letters). Other key endpoints included the percentage of patients who maintained q12w dosing through week 48 and anatomic outcomes. Results: At week 48, each brolucizumab arm demonstrated noninferiority to aflibercept in BCVA change from baseline (least-squares [LS] mean, +6.6 [6 mg] and +6.1 [3 mg] letters with brolucizumab vs. +6.8 letters with aflibercept [HAWK]; +6.9 [brolucizumab 6 mg] vs. +7.6 [aflibercept] letters [HARRIER]; P < 0.001 for each comparison). Greater than 50% of brolucizumab 6 mg-treated eyes were maintained on q12w dosing through week 48 (56% [HAWK] and 51% [HARRIER]). At week 16, after identical treatment exposure, fewer brolucizumab 6 mg-treated eyes had disease activity versus aflibercept in HAWK (24.0% vs. 34.5%; P = 0.001) and HARRIER (22.7% vs. 32.2%; P = 0.002). Greater central subfield thickness reductions from baseline to week 48 were observed with brolucizumab 6 mg versus aflibercept in HAWK (LS mean: −172.8 μm vs. −143.7 μm; P = 0.001) and HARRIER (LS mean: −193.8 μm vs. −143.9 μm; P < 0.001). Anatomic retinal fluid outcomes favored brolucizumab over aflibercept. Overall, adverse event rates were generally similar to brolucizumab and aflibercept.

Take-home message

Broculizumab is a novel humanized single-chain antibody fragment (scFv) Food and Drug Administration approved for the treatment of neovascular AMD. Being a scFv, it allows for delivery of greater molar dose compared to larger molecules, as well as much effective tissue penetration. HAWK and HARRIER, the Phase 3 trials comparing broculizumab q12w/q8w to aflibercept q8w, showed the former to be noninferior in terms of BCVA at 48 weeks. Anatomic outcomes favored broculizumab, owing to better tissue penetration. The overall safety profile was comparable to aflibercept.

  Universal Artificial Intelligence Platform for Collaborative Management of Cataracts Top

Wu X, Huang Y, Liu Z, Lai W, Long E, Zhang K, et al. Universal artificial intelligence platform for collaborative management of cataracts. Br J Ophthalmol 2019;103:1553-60.

Purpose:The purpose of this study was to establish and validate a universal artificial intelligence (AI) platform for collaborative management of cataracts involving multilevel clinical scenarios and explore an AI-based medical referral pattern to improve collaborative efficiency and resource coverage. Methods: The training and validation datasets were derived from the Chinese Medical Alliance for Artificial Intelligence (CMAAI), covering multilevel health-care facilities and capture modes. The datasets were labeled using a three-step strategy: (1) capture mode recognition; (2) cataract diagnosis as a normal lens, a cataract, or a postoperative eye; and (3) detection of referable cataracts with respect to etiology and severity. Moreover, we integrated the cataract AI agent with a real-world multilevel referral pattern involving self-monitoring at home, primary health care, and specialized hospital services. Results: The universal AI platform and multilevel collaborative pattern showed robust diagnostic performance in three-step tasks: (1) capture mode recognition (area under the curve [AUC]: 99.28%–99.71%), (2) cataract diagnosis (normal lens, cataract, or postoperative eye with AUCs of 99.82%, 99.96%, and 99.93% for mydriatic-slit-lamp mode and AUCs >99% for other capture modes), and (3) detection of referable cataracts (AUCs >91% in all tests). In the real-world tertiary referral pattern, the agent suggested 30.3% of people be “referred,” substantially increasing the ophthalmologist-to-population service ratio by 10.2-fold compared with the traditional pattern.

Take-home message

AI has made several breakthroughs in the field of medicine and health care. This study validated an effective and robust deep learning algorithm for image recognition, diagnosis, and referral of cataracts based on etiology and severity. The authors claim that this study has used the largest slit-lamp photography database till date with 37,638 photographs of normal and cataractous lenses of various etiologies and severities obtained from an ongoing Chinese cataract screening program by the CMAAI. This AI agent uses four images (mydriatic/nonmydriatic in diffuse and slit mode) for cataract recognition and referral with good accuracy even in nonmydriatic modes, unlike mydriatic mode images alone being used in prior studies. This advantage may enable its use in real-world cataract screening scenarios. Since cataract contributes to a major chunk of global blindness, this tool can aid the clinician in balancing the unmet needs in the community by reducing cost, increasing the ophthalmologist-to-patient service ratio, and extending teleophthalmology to cataract management workflow.

  Optical Analysis and Reappraisal of the Peripheral Light-Focusing Theory of Nasal Pterygium Formation Top

King-Smith PE, Mauger TF, Begley CG, Tankam P. Optical analysis and reappraisal of the peripheral light focusing theory of nasal pterygia formation. Invest Ophthalmol Vis Sci 2020;61:42.

Purpose: Pterygia are much more common nasally than temporally. Ultraviolet (UV) radiation is a major risk factor. Coroneo proposed that the nasal preference is caused by the “peripheral light-focusing (PLF) effect,” in which UV at an oblique angle passes through temporal cornea and is concentrated on and damages nasal limbal stem cells. This study evaluates whether the PLF is sufficient to explain the nasal preference. Methods: Whereas Coroneo et al. derived the maximum PLF intensity gain (UV concentration factor) as a function of incident angle (i.e., different nasal limbal positions were used for different incident angles), the current analysis derived intensity gain at a fixed position such at the nasal corneolimbal junction (CLJ). This provided a measure of the total PLF irradiation at this position, which was compared to total direct irradiation of nasal and temporal limbus at the corresponding positions (e.g., CLJs). In Part 1, the analysis was performed like that of Coroneo, using horizontally incident UV; in Part 2, the analysis was extended to include incident rays above and below the horizontal. Results: In both Part 1 and Part 2 of the study, the limbal UV irradiation of the nasal limbus from the PLF was not sufficient to explain the strong nasal location preference of pterygia.

Take-home message

Pterygia are common conjunctival pathology encountered in tropical areas due to high UV radiation exposure. It has a 15-fold increased nasal preference, its cause being still under debate. Coroneo et al. had suggested PLF to the nasal limbus as a reason for its nasal predilection. However, in this study, the authors point out that PLF at the nasal limbus was not a satisfactory explanation in itself to explain the strong nasal preference. The authors concluded that the site preference of the lesion needs more studies and suggested consideration of factors such as temporal-to-nasal tear flow increasing cytokine concentration at the nasal limbus and tear composition abnormalities as contributory to pterygia development.

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