Medical hypothesis discovery and innovation in ophthalmology

Background: The association between keratoconus and thyroid gland dysfunction (TGD) remains controversial. We aimed to determine the frequency of keratoconus among patients with laboratory-confirmed, treatment-naive TGD compared with that of age- and sex-matched healthy controls. Moreover, we investigated the potential relationship between TGD and corneal topographic and tomographic parameters.
Methods: This multicenter, cross-sectional study recruited individuals with treatment-naive, laboratory-confirmed TGD and sex- and age-matched healthy controls. Demographic and ophthalmic data of all participants were recorded. All participants underwent comprehensive ocular examinations and corneal tomography. Patterns of symmetric bowtie, asymmetric bowtie, asymmetric bowtie/superior steep, asymmetric bowtie/inferior steep, or asymmetric bowtie pattern with a skewed radial axis were documented if present. Furthermore, the maximum simulated keratometry value (Kmax), corneal thinnest thickness (CTT), and back elevation (BE) values were recorded. We measured the serum concentrations of thyroid-stimulating hormone (TSH) and thyroid hormones (free thyroxine [FT4] and free tri-iodothyronine [FT3]) using an immunoassay method.
Results: We included 200 eyes of 200 individuals with TGD and 200 eyes of 200 healthy age- and sex-matched controls, with female predominance in both groups. The mean FT4 concentration was significantly higher and the TSH concentration was significantly lower in the TGD group than in the control group (both P < 0.0001), whereas the FT3 level was comparable between groups (P > 0.05). In the TGD group, the frequencies of hyperthyroidism and hypothyroidism were 190 (95%) and 10 (5%), respectively. We found significantly lower mean CTT, higher Kmax, and greater BE values with a significantly higher frequency of abnormal topographic patterns among eyes in the TGD group than in controls (all P < 0.05). The frequency of eyes with keratoconus was significantly higher in the TGD (7.5%) group than in the control (0.5%) group (P < 0.0001). Except for a statistically significant correlation of Kmax (r = - 0.23, P < 0.05) and CTT (r = + 0.15, P < 0.05) with TSH level in the TGD group, no significant correlation was found between corneal characteristics and thyroid profile in either group (all P > 0.05).
Conclusions: We observed a higher frequency of keratoconus, with female predominance, in the TGD group. TGD was associated with significant changes in certain corneal topographic and tomographic parameters. Compared with healthy controls, individuals with TGD demonstrated increased Kmax and BE values with more corneal thinning, highlighting the potential association between keratoconus and TGD. However, further large-scale longitudinal studies are essential to confirm our findings.

Background: Astigmatism is the most prevalent refractive error among children and adults, and it can lead to visual impairment if left uncorrected. The management of compound hyperopic astigmatism is more challenging. This study presents the 12-month outcomes of toric implantable collamer lens (ICL) implantation in eyes with hyperopic astigmatism.
Methods: This interventional case series included patients with simple or compound hyperopic astigmatism who underwent toric ICL implantation. All eligible individuals underwent a detailed ocular examination. Uncorrected and corrected distance visual acuity (UDVA and CDVA, respectively), intraocular pressure, and manifest and cycloplegic refraction results were documented. Pentacam corneal tomography was performed to assess the central corneal thickness, iridocorneal angle width, and anterior chamber depth. Endothelioscopy was performed to determine endothelial cell density. The ICL V4b model was implanted in all the included eyes. Safety and efficacy indices were calculated as postoperative CDVA/preoperative CDVA and postoperative UDVA/preoperative CDVA, respectively.
Results: Twenty-six eyes with low-grade simple or compound hyperopic astigmatism were included. All eyes experienced a significant improvement of four lines in postoperative UDVA (P < 0.001), and their postoperative CDVA remained stable at the 12-month follow-up (P > 0.05). The safety and efficacy indices were 1.0. None of the eyes lost two or more lines of CDVA; in 81% of the eyes, CDVA was unchanged, and the proportion of eyes with 20/30 or better postoperative UDVA was identical to that with 20/30 or better preoperative CDVA (81% for each). The mean manifest spherical equivalent at the 12-month postoperative visit had significantly improved (P < 0.001). The percentages of eyes with postoperative spherical equivalent within ± 0.50 D and ± 1.00 D were 81% and 96%, respectively. The postoperative refractive cylinder improved significantly (P < 0.05), and the percentage of eyes with refractive cylinder within ± 0.50 DC and ± 1.00 DC were 50% and 77%, respectively.
Conclusions: Our outcomes indicate that toric ICL implantation is safe and effective for managing low-grade simple or compound hyperopic astigmatism. The proportion of eyes with 20/30 or better postoperative UDVA was identical to that with a 20/30 or better preoperative CDVA. The manifest spherical equivalent and refractive cylinder were significantly reduced. No serious safety concerns were observed. Further prospective large-scale studies with a wide range of ages and grades of hyperopic astigmatism are required to verify these preliminary outcomes.

Background: Panretinal photocoagulation (PRP) impacts macular function in eyes with early proliferative diabetic retinopathy (PDR). Herein, we used the multifocal electroretinogram (mfERG) to objectively investigate this concept.
Methods: In this prospective interventional case series, we enrolled patients with treatment-naive early PDR, absence of clinically significant macular edema, and requirement for PRP. All participants underwent detailed ocular examinations. We measured the best-corrected distance visual acuity (BCDVA), conducted optical coherence tomography imaging to measure central macular thickness (CMT), and performed mfERG at baseline and 3 months post-PRP. Amplitude and latency of the mfERG response were evaluated within the innermost four of the five concentric rings.
Results: We enrolled 29 eyes of 23 patients with a mean (standard deviation) age of 54.3 (8.8) years and male-to-female ratio of 1:1.3. The mean BCDVA was unchanged post-treatment (P >0.05), and the BCDVA in 26 eyes (89.7%) was either improved or unchanged, whereas in three eyes (10.3%) it decreased. The mean CMT was unchanged post-PRP (P >0.05). Concerning the mfERG, the mean P1 amplitudes decreased significantly in all four concentric rings from the foveola at 3 months post-PRP compared with baseline values (all P <0.05); however, the latencies were unchanged (all P >0.05). At baseline, BCDVA correlated significantly with both the amplitude (r = + 0.55; P <0.05) and latency (r = - 0.38; P <0.05) of the mfERG in the central ring, whereas a significant correlation was detected with only the amplitude at 3 months post-PRP (r = + 0.52; P <0.05).
Conclusions: Macular function was decreased 3 months post-PRP in patients with early PDR, as indicated by decreased amplitude of the mfERG, whereas the functional and anatomical parameters were stable. The mfERG served as an objective tool for measuring retinal function and predicting visual outcomes post-PRP in eyes with early PDR. A higher amplitude in the mfERG correlated substantially with a better visual outcome post-PRP. Further multi-center longitudinal studies with robust designs including different PDR severity levels may reveal additional objective aftereffects of PRP.

Background: The intraretinal hyperreflective line (IHL) is a novel posterior segment finding demonstrable using careful optical coherence tomography (OCT) examination. It likely indicates a reaction against photoreceptor, Muller cell, and/or retinal pigment epithelial damage. This study analyzed the spectral-domain OCT characteristics of IHLs to disclose their presence in various retinal conditions.
Methods: A retrospective review of the charted and imaging records of participants with IHL was conducted at Dokuz Eylul University Department of Ophthalmology between January 2019 and August 2023. The inclusion criterion was the detection of an IHL on good-quality B-scan spectral-domain OCT. An IHL was defined as a vertical line extending from the ellipsoid zone band (or lower) through the outer nuclear layer to the internal limiting membrane in the central fovea. Associated retinal conditions were recorded as potential causative factors for the presence of IHL.
Results: IHL was observed on spectral-domain OCT in 40 eyes of 38 participants with several retinal diseases assessment. Fourteen eyes (35%) underwent vitreoretinal surgery pre-IHL detection (12 were operated for full-thickness macular hole [FTMH], one for epiretinal membrane [ERM], and one for rhegmatogenous retinal detachment). In six eyes (15%) a microhole coexisted. Four eyes (10%) had a concurrent lamellar macular hole. The IHL preceded the occurrence of FTMH in three eyes (7.5%), and diabetic macular edema and type 2 idiopathic macular telangiectasia (MacTel-2) were present in three eyes (7.5%) each. The remaining conditions included vitreomacular traction (VMT), non-arteritic anterior ischemic optic neuropathy with central retinal artery occlusion, commotio retinae, exudative age-related macular degeneration, ERM, non-infectious idiopathic posterior uveitis, and Coats’ disease, each affecting one eye (2.5%). Of the two participants with bilateral involvement, one was diagnosed with MacTel-2 and the other had IHL with VMT in the right eye that was detected post-vitreoretinal surgery for FTMH in the left eye.
Conclusions: Although IHLs are mostly identified in eyes with vitreomacular surface diseases, clinicians may encounter IHLs in other types of retinal pathology. Further large-scale, multicenter, long-term studies on the presence of IHLs in OCT imaging are required to provide more substantial insight on this biomarker.

Background: Age-related macular degeneration (ARMD) leads to impaired vision and potential blindness. Globally, it accounts for approximately 9% of vision loss cases, and a projected 288 million individuals will be affected by 2040. Current treatments have limitations such as variable effectiveness, high costs, and potential side effects. Additionally, atrophic ARMD management remains challenging. As saffron has shown promising neuroprotective and antioxidant effects by potentially delaying disease progression, this study aims to review the mechanistic, pre-clinical, and clinical evidence of the effects, safety, and tolerability of saffron in ARMD treatment.
Methods: The Scale for the Assessment of Narrative Review Articles was applied in this narrative review. To find relevant literature, the syntax “(saffron OR crocus) AND (retin* OR “geographic atrophy” OR “choroidal neovascular*” OR “macular degeneration”)” was searched in PubMed/MEDLINE. Pre-clinical and clinical original investigations of the effects of saffron in ARMD along with the eligible studies cited in their reference lists were identified and included.
Results: Saffron and its active compounds, crocin and crocetin, have shown promising results in improving visual function and delaying ARMD progression. Several clinical studies have found that daily supplementation with 20–50 mg of saffron or 5–15 mg of crocin for 3–12 months significantly improved best-corrected visual acuity, contrast sensitivity, and retinal function as measured by electroretinogram and microperimetry, with benefits observed in both dry and wet forms of ARMD. The effects were independent of genetic risk factors and maintained during the follow-up periods, suggesting the potential role of saffron as a long-term treatment option. Saffron reduces ARMD progression via anti-angiogenic, neuroprotective, and antioxidant mechanisms. Moreover, saffron is safe and well tolerated.
Conclusions: Although further research is needed to confirm long-term safety and efficacy, current evidence supports the use of saffron or crocin supplements as a safe and tolerable adjunct therapy for ARMD management.

Background: Linear-regression analysis is a well-known statistical technique that serves as a basis for understanding the relationships between variables. Its simplicity and interpretability render it the preferred choice in healthcare research, including vision science, as it enables researchers and practitioners to model and predict outcomes effectively. This article presents the fundamentals of linear-regression modeling and reviews the applications and interpretations of the main linear-regression analysis.
Methods: The primary objective of linear regression is to fit a linear equation to observed data, thus allowing one to predict and interpret the effects of predictor variables. A simple linear regression involves a single independent variable, whereas multiple linear regression includes multiple predictors. A linear-regression model is used to identify the general underlying pattern connecting independent and dependent variables, prove the relationship between these variables, and predict the dependent variables for a specified value of the independent variables. This review demonstrates the appropriate interpretation of linear-regression results using examples from publications in the field of vision science.
Results: Simple and multiple linear regressions are performed, with emphasis on the correct interpretation of standardized and unstandardized regression coefficients, the coefficient of determination, the method for variable selection, assumptions in linear regression, dummy variables, and sample size, along with common mistakes in reporting linear-regression analysis. Finally, a checklist is presented to the editors and peer reviewers for a systematic assessment of submissions that used linear-regression models.
Conclusions: Medical practitioners and researchers should acquire basic knowledge of linear-regression such that they can contribute meaningfully to the development of technology by accurately interpreting research outcomes. Incorrect use or interpretation of appropriate linear-regression models may result in inaccurate results. Appointing an expert statistician in an interdisciplinary research team may offer added value to the study design by preventing overstated results.