Medical hypothesis discovery and innovation in ophthalmology

Background: Monotherapy, age, and side effects are significant risk factors for the discontinuation of antiglaucoma therapy. Long-term therapy persistence is crucial for slowing disease progression and preventing irreversible blindness. Therefore, it is essential to identify patients at higher risk of discontinuation. In this study, we aimed to evaluate the real-world persistence of antiglaucoma therapy in patients diagnosed with glaucoma in the primary healthcare units of the Lisbon and Tagus Valley regions.
Methods: We conducted a retrospective longitudinal study by collecting data from the prescription records of new antiglaucoma drug users diagnosed with glaucoma between 2012 and 2013 in the Primary Health Care Units of the Lisbon and Tagus Valley Region. These patients were followed over 3 years. Therapy persistence was measured as the proportion of patients remaining on any antiglaucoma drug, regardless of any modifications or switching of drugs over time. Persistence was assessed at three time points: the end of the first, second, and third years of the observation period.
Results: A total of 2138 patients treated using new antiglaucoma drugs (867 [40.6%] male patients; 1271 [59.4%] female patients) were included in the study. Over the observation period, the overall persistence rate decreased from 91.9% (n = 1965) in the first year to 67.3% (n = 1439) in the third year. Older patients (greater than or equal to 65 years) showed higher persistence rates, although there was a decrease over the 3-year follow-up period (from 1481 [92.7%] to 1124 [70.4%]). Additionally, participants initially treated with monotherapy showed higher persistence rates, ranging from 92.4% (n = 1186) in the first year to 70.2% (n = 901) in the third year.
Conclusions: The findings highlight the importance of patient follow-up over time, as almost one in three new antiglaucoma therapy users completely discontinued treatment, potentially risking disease progression. This could be mitigated with proper use of these drugs. Further studies should utilize recent health information systems to explore the impact of medication adherence and persistence on the functional and structural outcomes in patients with glaucoma.

Background: Pseudoexfoliation syndrome (PES) is an age-related systemic condition that predominantly affects ocular structures and is characterized by the deposition of material on the lens, ciliary body, zonules, corneal endothelium, iris, and pupillary margin. We compared the corneal endothelial morphology, anterior segment parameters, corneal densitometry, and corneal topographic characteristics between the clinically affected and apparently normal fellow eyes of patients with clinically unilateral PES.
Methods: This was a comparative, cross-sectional study of 34 patients with clinically unilateral PES. The anterior segment was examined using a Scheimpflug imaging system, and the corneal endothelium was assessed using a noncontact specular microscope. Corneal endothelial cell density, polymegathism, and pleomorphism were assessed using the specular microscope. Furthermore, the Scheimpflug camera was used to measure the corneal power of the flat and steep axis, mean corneal power, maximum keratometry, anterior chamber angle, anterior chamber depth, anterior chamber volume, corneal volume, and the corneal thickness at the apex point, center of the pupil, and the thinnest point. Corneal densitometry was evaluated at two concentric zones (0–2 mm and 0–12 mm).
Results: In total, 68 eyes from 34 patients were ultimately included in the study. The mean (standard deviation) age of the patients was 73.38 (8.75) years (range: 50–87 years). Among the included patients, 17 (50%) were male and 17 (50%) were female. The anterior segment parameters did not significantly differ between eyes with PES and their clinically unaffected fellow eyes (all P > 0.05). Similarly, no statistically significant difference was observed in corneal endothelial morphology (all P > 0.05).
Conclusions: Our measured parameters do not differ between the clinically affected eye and the clinically unaffected fellow eye. This supports the theory that PES is a bilateral disorder. Considering the variety of complications associated with PES, bilateral involvement should be assumed in the clinical and surgical management of patients with clinically unilateral PES. In the future, new research could increase our understanding of this syndrome.

Background: The effects of trabeculectomy on anterior segment parameters have been widely investigated. However, the stabilization time for various glaucoma types after trabeculectomy remains debatable. We investigated the effect of mitomycin C-augmented trabeculectomy on ocular anterior segment parameters in primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (PXG) during short-term follow-up using the Pentacam HR.
Methods: In this retrospective observational study, consecutive patients diagnosed with medically uncontrolled POAG or PXG who underwent MMC-augmented trabeculectomy were recruited. All individuals underwent detailed ocular examinations. All trabeculectomies were performed by a single surgeon using the same technique. Anterior segment parameters, including anterior chamber depth (ACD), anterior chamber volume (ACV), anterior chamber angle (ACA), and central corneal thickness (CCT) were measured using the Pentacam HR, along with intraocular pressure (IOP) using a Goldmann applanation tonometer, pre-operatively and at 1-week, 1-month, and 3-month post-operative visits.
Results: We included 80 patients with a median (range) age of 58.0 (41.0–86.0) years having a nearly similar sex ratio. The study groups were matched according to sex and age (both P > 0.05). The group-by-time interaction was significant for CCT and ACV (both P < 0.05) but not for IOP, ACD, and ACA (all P > 0.05). The mean (standard deviation [SD]) IOP, ACD, and ACA were comparable between groups (all P > 0.05) during the 3-month period; however, they changed significantly over time in both groups (all P < 0.001). The mean CCT and ACV were comparable between groups at each time point (all P > 0.05), except at the 1-month post-operative visit, at which the mean (SD) ACV was significantly lower in the PXG group (P < 0.05). We found a comparable mean (SD) CCT between paired visits in each group (all P > 0.05), except for the mean (SD) CCT at 3 months, which was significantly lower than that at the 1-month post-operative visit in the PXG group (P < 0.05). We found a comparable mean (SD) ACV between paired visits in each group (all P > 0.05); however, it was significantly lower at the 1-month post-operative versus the baseline visit in both groups and resumed a significantly higher value at the 1-month versus the 1-week visit and at the 3-month versus the 1-month visit in the PXG group (all P < 0.05).
Conclusions: We observed significant changes in IOP, ACD, and ACA over 3 months after post-augmented trabeculectomy in eyes with POAG and PXG; however, the majority of anterior segment parameters were comparable between the two groups. Further large-scale studies with longer follow-up periods should be conducted to verify the post-operative fluctuations in these parameters in POAG and PXG.

Background: Strengthening of extraocular muscles is a conventional procedure in the management of strabismus. Plication may be an alternative strengthening technique, and is less invasive than resection. This study compared plication and resection, each combined with antagonist muscle recession, in terms of success rates and changes in ocular deviation in the management of horizontal strabismus.
Methods: This retrospective study recruited individuals with horizontal strabismus who underwent plication (group I) or resection (group II) coupled with antagonist muscle recession. All participants underwent a detailed baseline eye and ocular motility evaluation. Demographic and clinical data were collected, including age, sex, type of preoperative strabismus (exotropia or esotropia), baseline visual acuity, mean follow-up duration, laterality of operated eye, surgical doses of correction (resection, plication, or recession) in millimeters, preoperative strabismus magnitude in prism diopters (PD), and postoperative strabismus magnitude in PD. Successful postoperative deviation was defined as less than or equal to 10 PD. At final follow-up, the success rates and degrees of change in angle of deviation were recorded.
Results: Forty-four patients were enrolled: 19 patients in group I (plication) and 25 patients in group II (resection). The groups had comparable ages, sex ratios, types of strabismus, and preoperative and postoperative angles of deviation (all P > 0.05). Despite comparable success rates between groups (73.7% in group I versus 64.0% in group II, P > 0.05), the difference (9.7%) was marginally close to the predefined clinically meaningful difference of 10%. In the esotropia subgroup, despite comparable alignment between the plication and resection groups (P > 0.05), the difference was clinically meaningful (17.3%), and both groups had higher success rates in the esotropia subtype than in the exotropia subtype. The rate of over- or undercorrection was not statistically or clinically different in the total and in each subtype of strabismus (all P > 0.05). Success rates for unilateral and bilateral cases were similar between groups (both P > 0.05). Changes in angle of deviation were similar for individuals with esotropia and exotropia between groups (both P > 0.05).
Conclusions: In esotropic and exotropic strabismus, plication and resection procedures combined with antagonist recession were similarly effective. However, further randomized, large-scale, longitudinal studies with clinical and subjective evaluations could provide practical evidence on the suitability of the plication procedure in managing various types of strabismus.

Background: Children with autism spectrum disorder (ASD) may have impaired vision owing to high refractive errors and aversion to spectacles or contact lenses. Visual blurring is caused by near-sighted myopia, far-sighted hyperopia, or astigmatism in one or both eyes. Refractive surgery can restore sharp vision and eliminate the need for spectacles and contact lenses. Restoration of sharp vision may improve ASD behavior. We aimed to determine the refractive outcomes in this cohort using ophthalmic measures and behavioral and school performance alterations after refractive surgery by employing parent–proxy reports.
Methods: This interventional, retrospective case series included data from 267 children with refractive errors and neurodevelopmental disorders (NDDs) diagnosed as ASD alone or NDD with ASD-like behaviors over a 15-year period. One of three refractive surgery methods was employed, with the choice of method uniquely tailored to the child’s eye anatomy. Laser photorefractive keratectomy (PRK) was performed in 131 children, implantation of a phakic intraocular lens (pIOL) in 115 children, and removal of the crystalline lens and implantation of an intraocular lens (refractive lens exchange, RLE) in 21 children. All procedures were performed under brief general anesthesia, with the child returning home on the same day.
Results: The median age at surgery was 10.9 years and the median follow-up period was 3.1 years. Pre-operative refractive errors ranged from a mean (standard deviation) +7.5 (0.09) D to -14.3 (4.8) D. Surgery corrected 87% of the children to normal focal length (± 1 D). Visual acuity improved an average of 0.6 logarithm of the minimum angle of resolution, the equivalent of 6 lines on a standard eye chart. Change in visual acuity was significant (all P < 0.01) between baseline and the most recent follow-up examination in each of subgroups. Change in spherical equivalent refractive error at 3, 12, 24, 36, 60, and > 60 months post-operatively were significant (all P < 0.01) between baseline and each follow-up visit in each of subgroups. Social interactions and ASD behaviors improved in 72% (192) of the treated children (P < 0.01). The incidence of sight-threatening complications was low.
Conclusions: Refractive surgery improves both visual function and behavior in most children with ASD and major myopia, hyperopia, or astigmatism. The PRK, pIOL, and RLE procedures appear to be effective and reasonably safe methods for improving refractive error, visual acuity, and behavior in many ametropic children with ASD and ASD-like NDDs.

Background: Retinitis pigmentosa (RP) is an inherited retinal dystrophy characterized by progressive vision loss due to photoreceptor degeneration. Complicated cataract formation, particularly posterior subcapsular cataract (PSC), frequently occurs in RP and exacerbates the visual impairment. Cataract surgery may improve vision; however, the distinctive challenges of RP require specific considerations. This mini-review aims to provide a comprehensive overview of the RP-related cataract.
Methods: A comprehensive literature review was conducted via PubMed/MEDLINE, spanning the period from January 1976 to June 2024, using the keywords “cataract,” “cataract surgery,” “cystoid macular edema,” “hereditary retinal dystrophy,” “retinitis pigmentosa,” “posterior subcapsular cataract,” “posterior capsular opacification,” “zonular weakness,” and “artificial intelligence.” We aimed to evaluate cataract surgery in patients with RP, focusing on cataract formation, its surgical management, postoperative complications, patient follow-up, and visual outcomes. Relevant review articles, clinical trials, and case reports with related reference lists of these articles were included.
Results: A total of 53 articles were examined in detail, including those identified through focused keyword searches and the reference lists of these articles. Cataract surgery in patients with RP generally results in substantial visual improvement. However, surgery can be complicated, particularly by zonular weakness and subluxation of the crystalline lens. These risks can be reduced by using capsular tension rings and employing meticulous surgical technique. Furthermore, postoperative complications, such as cystoid macular edema and posterior capsular opacification, are common. Despite these challenges, regular postoperative follow-up and appropriate management can help mitigate complications. Integrity of the ellipsoid zone and external limiting membrane on preoperative optical coherence tomographic examination are the main predictors of visual outcomes following cataract surgery; however, outcomes can vary. Though many patients experience significant visual improvement, some may experience limited benefits due to pre-existing advanced retinal degeneration.
Conclusions: Cataract surgery may offer meaningful visual benefits in patients with RP; however, careful preoperative evaluation and meticulous surgical technique are required to address the possible challenges. Attentive postoperative care and follow-up are essential to optimize visual outcomes. Early surgical intervention can significantly improve the quality of life in selected candidates, and tailored approaches are necessary in patients with RP requiring cataract surgery. Further studies on the potential application of artificial intelligence to monitor postoperative recovery and detect complications may improve surgical outcomes and enhance patient care.