Medical hypothesis, discovery & innovation in optometry

Background: Currently, hyaluronic acid (HA) and carboxymethyl cellulose sodium (CMC) are common polymers incorporated in artificial tears (ATs). The aim of the present study was to evaluate the immediate effect of preservative- and preservative-free HA- and CMC-containing ATs on tear-film parameters and determine patient preference after AT instillation.
Methods: In this prospective, double-blind, randomized, comparative study, we assessed fluorescein tear break-up time (TBUT), bulbar redness, and tear ferning pattern (TFP) up to 60 min after the instillation of ATs with and without preservatives containing HA and CMC in the recruited participants. To test patient preference, each patient was administered with the Ora Calibra™ Ocular Discomfort and 4-Symptom Questionnaire (OOD4SQ; scale of 0–5) before and 60 min after the instillation of ATs. The selection of 14 descriptive words based the 11-point Ora Calibra™ Drop Comfort Scale (ODCS; scale of 0–10) was administered immediately after instillation of each AT to test the drop comfort score.
Results: We enrolled 200 eyes of 200 patients, including 163 (81.5%) women and 37 (18.5%) men, with a mean (standard deviation) age of 28.38 (5.42) years. Immediately or 5, 15, or 60 min after the instillation, the mean TBUT did not differ by presence of preservatives, HA, or CMC (all P > 0.05). However, it was significantly higher 5-min post-instillation compared to baseline and significantly lower 15- and 60-min post-instillation (all P < 0.05). The mean grade of bulbar redness immediately or 3, 5, 15, or 60 min after instillation did not differ by presence of preservatives for HA or CMC containing ATs (all P < 0.05). It did not differ significantly 3-, 5-, 15-, or 60-min post-instillation compared to baseline (all P > 0.05). The mean drop comfort scale after the instillation of ATs did not differ significantly by presence of preservatives, HA, or CMC (all P < 0.05). Positive descriptive words were selected by a higher proportion of participants in both groups. According to OOD4SQ, the overall discomfort and mean dryness scores improved significantly after instillation of HA-containing ATs (both P < 0.05), while the mean burning sensation, grittiness, and stinging scores remained unchanged (all P > 0.05). The overall discomfort and mean scores for each ocular symptom (P < 0.05), except for stinting (P > 0.05), improved significantly after instillation of CMC-containing ATs. The TFP did not change significantly from baseline to 60 min after the instillation of any AT (P > 0.05).
Conclusions: Both ATs with and without preservatives containing HA and CMC produced positive short-term objective and subjective effects. However, TBUT, TFP, bulbar redness, and patient feedback were comparable for both HA- and CMC-containing ATs. Further trials with longer observation periods or the recruitment of patients with different severities of dry eye could provide more robust and clinically applicable conclusions.

Background: Infants treated for retinopathy of prematurity (ROP) could develop visually significant refractive errors. In this study, we report pre-treatment refractive errors in premature infants with treatment-requiring ROP treated using laser or anti-VEGF monotherapy and compare the components of post-treatment refractive error values between the two treatment groups at different follow-up timepoints.
Methods: In this retrospective cohort study, we analyzed 360 eyes of 181 premature infants with treatment-requiring ROP who were referred to Farabi Eye Hospital, Tehran, Iran between March 2020 and April 2021. Of the 360 eyes, 195 received laser monotherapy (laser treatment group) and 165 received an intravitreal anti-VEGF injection (anti-VEGF therapy group). All included eyes underwent pre- and post-treatment cycloplegic refraction. Cycloplegia was induced for each infant by instilling a mixed eye drop containing 1% tropicamide, 2.5% phenylephrine, and 0.5% tetracaine (in equal volumes) in each eye three times at five-minute intervals. Cycloplegic refraction was performed 30 minutes after the third instillation.
Results: The mean (standard deviation [SD]) gestational age (GA) and birth weight (BW) of the infants were 29.0 (2.0) weeks and 1241.0 (403.0) g, respectively. The male-to-female ratio in the entire study cohort was 107 (59.1%) / 74 (40.9%), whereas the ratios in the anti-VEGF therapy group and laser treatment group were 47 (56.6%) / 36 (43.4%) and 60 (61.2%) / 38 (38.8%), respectively. The pre-treatment assessment revealed that 218 (60.6%) eyes were hyperopic, 112 (31.1%) were myopic, and 30 (8.3%) were emmetropic. In the anti-VEGF therapy group, 87 (52.7%) eyes were hyperopic, 63 (38.2%) were myopic, and 15 (9.1%) were emmetropic. In the laser treatment group, 131 (67.2%) eyes were hyperopic, 49 (25.1%) were myopic, and 15 (7.7%) were emmetropic. The mean (SD) spherical refractive error and spherical equivalent of refractive error (SEQ) at the 1-week, 1-month, and > 6-month post-treatment follow-up timepoints; the mean cylindrical refractive error at the 3-month post-treatment timepoint; and the mean SEQ at the time of ROP regression were significantly different between the treatment groups (all P < 0.05). The rate of anisometropia increased significantly from 3.4% at baseline to 9.2% at the 6-month post-treatment follow-up timepoint (P < 0.05).
Conclusions: In this study, the most common pre-treatment refractive status of all included eyes with treatment-requiring ROP and eyes in each treatment group was hyperopia, followed by myopia and emmetropia. At the more than 6-month post-treatment follow-up, cycloplegic refraction revealed that the laser-treated eyes were significantly more hyperopic than the anti-VEGF-treated eyes, a finding similar to the pre-treatment refraction results. Further studies of same cohort with a longer follow-up period and a control group are needed to determine the real-world effect of each treatment modality on the refractive statuses of children treated for ROP.

Background: Orbital decompression is frequently indicated to treat exophthalmos and compressive optic neuropathy, among other indications for thyroid eye disease (TED). This study aimed to evaluate the outcomes of orbital decompression and compare the results by urgency and type of surgery in patients with TED.
Methods: In this cross-sectional study, we recruited patients with TED who had undergone emergency or elective orbital decompression surgery at a tertiary eye care referral center in Tehran, Iran, between 2010 and 2020. Ophthalmic examination findings, demographic and clinical profiles, and types and outcomes of surgical interventions were reviewed and analyzed.
Results: Fifty-one orbits of 35 patients with a mean (standard deviation [SD]) age of 36.2 (12.0) years and male-to-female ratio of 23 (66%)/12 (34%) were included. The mean (SD) duration from the diagnosis to the surgery was 41.0 (39.0) months. The surgical method was fat decompression in 1 (2%) orbit; fat and inferior wall decompressions in 2 (4%) orbits; fat, inferior, and medial wall (two-wall) decompressions in 43 (84%) orbits; and fat, inferior, medial, and lateral wall (three-wall) decompressions in five (10%) orbits. Three-wall decompression surgery resulted in significantly lower exophthalmometry readings than those associated with two-wall surgery at all postoperative follow-ups (P < 0.05). Ten (20%) orbits required emergency decompression because of sight-threatening conditions and revealed comparable exophthalmometry readings with electively decompressed orbits at the 1-year visit (P > 0.05). Thirty-seven (73%) orbits required other surgeries within the 1-year follow-up. The mean (SD) exophthalmometry readings before and 1-year after surgery were 26.3 (4.0) and 18.3 (2.7) mm, respectively, with a significant decrease and significant 5.5 (3.3)-mm change from baseline in decompressed orbits (both P < 0.001). Diplopia was reported in 29% (n = 10) of patients less than 2 months postoperatively.
Conclusions: Emergency or elective orbital decompression significantly reduced exophthalmos in patients with TED within 1 year postoperatively. Three-wall orbital decompression produced the more immediate impact, while two-wall orbital decompression showed the higher effect at a later timepoint. The most common complication was diplopia, while other serious complications occurred infrequently. Further prospective comparative studies involving more participants and longer postoperative follow-up periods are required to verify these preliminary findings.

Background: The association between metformin use and reduced age-related macular degeneration (AMD) risk has been explored. Studies have shown a positive association, no association, or ambiguous results. The aim of this narrative review is to compile these divergent findings, and thereby, better assess the potential of metformin use in reducing the AMD risk.
Methods: Studies were extracted in two ways. First, a standard Google Scholar™ search was performed using the keywords “metformin” AND “macular degeneration” without language or time restrictions. The full texts of relevant articles identified in this search were retrieved and assessed, and articles of peer-reviewed original studies and meta-analyses were included. Second, the reference lists of the included articles were used to identify additional articles that satisfied the search algorithm and included in this review.
Results: Of the 12 studies included in this review, eight showed a positive correlation between metformin use and a reduced AMD risk, while one showed no association. Of the eight positive studies, seven were retrospective. Apart from the design, the studies were also diverse. The number of participants in each study ranged from over 300 to 30 million person-years. The study populations included those with type 2 diabetes mellitus, those with AMD, and those without either. The study locations were the United States, Europe, and Asia. The ambiguous or negative results from four studies could largely be rationalized based on the confounding factor of study design.
Conclusions: Most studies examined in this review demonstrated a positive association between metformin use and a reduced AMD risk. Studies not reporting such an association did not definitively demonstrate its absence. Overall, the studies reviewed herein support further clinical investigation of metformin as a prophylactic and potential treatment modality for AMD. Further randomized clinical trials with reasonably longer follow-up periods are necessary to determine the generalizability of the findings of studies reporting positive results.

Background: Putative adverse effects of prostaglandin analogs in patients treated for glaucoma include periocular skin darkening, herpes simplex keratitis, cystoid macular edema, iritis, and headaches. Here, we report a case of migraine headache after a travoprost administration and discuss the role of prostaglandin analogs in migraine-like headaches.
Case Presentation: A 70-year-old man visited the hospital complaining of pain, redness, and sensitivity to light for 1 week associated with gradual loss of vision in the right eye after cataract surgery, which had been performed 2 years prior. After the examination, the patient was diagnosed with pseudophakic bullous keratopathy and advised to undergo optical penetrating keratoplasty of the right eye. On postoperative day 3, his intraocular pressure (IOP) was 30 mmHg at 10:00 AM in the right eye. A single dose of 0.004% travoprost was instilled in the right eye on the same day. His IOP decreased to 16 mmHg at 2:00 PM. The next day, he presented with migraine-like headache that had started within 1 h after the instillation the previous night. Unremarkable neurological examination and neuroimaging suggested that travoprost had caused the migraine. Although the headache gradually resolved, it reappeared after the administration of other prostaglandins. Trabeculectomy was performed on the right side. The IOP was controlled, and the headache was resolved.
Conclusions: This case indicates a potential causal relationship between topical prostaglandin analogs and migraine-like headaches, as evidenced by symptom resolution upon discontinuation. However, large-scale studies including control groups are required to prove a causal relationship between topical prostaglandin analog administrations and headache development.

Background: Radiation retinopathy is a major cause of vision loss in patients receiving radiotherapy to the head and orbit. Diabetic retinopathy is one of the differential diagnosis owing to similar clinical features, including microaneurysms, cotton-wool spots, hard exudates, and macular edema. The only significant pathological difference is that radiation retinopathy spares pericytes, unlike in diabetic retinopathy. Multimodal imaging helps diagnose and predict the prognosis of radiation retinopathy, which is presented in this case report.
Case Presentation: A 55-year-old woman diagnosed with stage-4 metastatic breast carcinoma presented with gradual diminution of vision in the left eye (OS) over 5 months. Vision in the right eye was lost because of orbital radiotherapy for orbital metastasis. The patient underwent multiple sessions of chemotherapy and radiotherapy. Examination of the left eye revealed a best-corrected distance visual acuity (BCDVA) of 20/30. Fundus examination of the OS revealed multiple cotton-wool spots and retinal hemorrhages. Fundus fluorescein angiography (FFA) showed diffuse macular leakage with capillary nonperfusion. Multicolor imaging (MCI) with Spectralis™ revealed black dots in the blue and green reflectance images, corresponding to capillary dilatation on FFA. Darker dots were more evident in the infrared images. BCDVA improved to 20/20 in OS after tapering the dose of oral steroids for 2 months, with improvements in hemorrhages and cotton-wool spots. Focal laser photocoagulation was recommended for the treatment of persistent macular edema. The patient declined further treatment, was lost to follow-up, and passed away 6 months later.
Conclusions: This case highlights the importance of multimodal imaging for the identification and classification of radiation retinopathy. MCI using SpectralisTM has been described for the first time in radiation retinopathy and can be used to complement existing imaging modalities. Future studies involving more patients and a longer follow-up duration may provide better results for the applicability of these imaging modalities in the clinical setting.