Medical hypothesis, discovery & innovation in optometry

Background: Flap creation during laser refractive surgery restructures the anterior cornea, particularly the stroma, reducing the keratocyte cell density (KCD). This reduced density makes it challenging to completely regenerate to the presurgical phase. The aim of the present study was to investigate the effects of two types of artificial tear (AT) interventions on KCD up to 3 months after femtosecond laser-assisted in situ keratomileusis (FS-LASIK) surgery.
Methods: This prospective, double-blind, comparative, interventional, contralateral eye study recruited patients with myopia scheduled for FS-LASIK. Inclusion criteria were healthy individuals aged 19 – 25 years with moderate or high myopia, a maximum cylindrical error of - 1.25 diopters, and a maximum pupil size of 6.5 mm who had undergone FS-LASIK and completed 3 months of follow-up. Complete optometric and ophthalmologic examinations were performed. Bilateral simultaneous FS-LASIK surgery was performed using the same femtosecond laser platform as in the standard procedure. The Research Randomizer was used to determine the eye to be treated with Systane® Hydration (Alcon Laboratories, Inc., Fort Worth, TX, USA) or Systane® ULTRA (Alcon Laboratories, Inc., Fort Worth, TX, USA) AT. KCD was examined using real-time images obtained from in vivo confocal microscopy (Heidelberg Retina Tomograph 3 with the Rostock Cornea Module, HRT III RCM); Heidelberg Engineering GmbH, Heidelberg, Germany) at baseline and 1- and 3-month postoperative visits.
Results: We included 60 eyes of 30 participants with a mean (standard deviation) age of 21.34 (1.85) years and a male-to-female ratio of 1:1 who completed 3-month post-FS-LASIK surgery follow-up. KCD did not differ significantly between the two groups at any visit (all P > 0.05); nevertheless, mean KCD was initially reduced up to 1 month postoperatively and then revealed a slight increase up to 3 months postoperatively in Systane® Hydration-treated eyes and continued to reduce in Systane® ULTRA-treated eyes. Intragroup comparisons revealed that the eyes treated with ATs experienced a significant reduction in KCD between the preoperative and 1-month postoperative visits and between the preoperative and 3-month postoperative visits (all P < 0.05). Treatment-related complications were not observed.
Conclusions: Overall, KCD reduced up to 3 months post-FS-LASIK surgery. Both AT types exerted a comparable effect on postoperative KCD up to 3 months. Future studies with a more frequent administration of ATs, longer follow-up periods, and a control group are required before preliminary outcomes of the present study can be generalized.

Background: In rhegmatogenous retinal detachment (RRD), the risk of fellow eye involvement varies from 5% to 34% according to the follow-up duration and criteria used for patient selection. The aim of the present study was to investigate the frequency, characteristics, and predisposing factors for symmetric lesions in the fellow eyes of patients with RRD or retinal breaks.
Results: Of the 68 participants, with a mean (standard deviation) age of 48 (12.1) years, 54 (79.4%) were men, and 14 (20.6%) were women. Of the 68 primary eyes, 60 (88.2%) had RRDs, and eight (11.8%) had retinal breaks. Horseshoe tears were the main lesion in 41 (68.3 %) primary eyes with RRD. Symmetric lesions were observed in 37 (54.4%) fellow eyes, including retinal breaks in 16 (43.2%) and lattice degeneration without breaks in 21 (56.8%) eyes. Lattice degeneration and multiple breaks were observed in 15 of 28 (53.6%) primary eyes with a lattice, whereas only seven of 40 (17.5%) lattice-free primary eyes had multiple breaks (P = 0.002). A multiple logistic regression model revealed that the presence of lattice degeneration in the primary eye (odds ratio, 26.91; 95% confidence interval, 4.18 – 173.20; P < 0.001) was the only factor predicting symmetricity in the fellow eye.
Conclusions: More than half of the patients with RRD or retinal breaks in the primary eye harbored symmetrical retinal lesions in their fellow eyes. This emphasizes the importance of regular examination of the fellow eyes with a greater focus on symmetric positions in the fellow eye. The presence of a lattice in the primary eye was the only predictor of symmetry in the contralateral eye. Further longitudinal studies with larger populations are required to determine the significance of these symmetric lesions in the fellow eyes of patients with RRD and the value of prophylactic treatment.

Background: Systemic complications of intravitreal bevacizumab (IVB) injections have been previously reported. We aimed to summarize the systemic complications reported in online primary studies. Moreover, we describe a patient experiencing simultaneous renal and cutaneous drug-induced adverse effects, with exacerbation of chronic renal insufficiency and granulomatous skin lesions, after receiving several IVB injections to manage bilateral ischemic branch retinal vein occlusion (BRVO).
Case Presentation: A 69-year-old Hispanic diabetic man with chronic renal insufficiency due to polyclonal gammopathy received several IVB injections to treat bilateral ischemic BRVO. One week after the sixth injection, the patient developed acute-on-chronic renal failure and multiple rounded maculopapular, erythematous, and ulcerated skin lesions. Renal and skin biopsy specimens revealed granulomatous drug-induced responses in both organs, and granulomatous diseases of infectious and oncological sources were ruled out. We performed an electronic search of the PubMed/MEDLINE database with no language or time restrictions using the keywords “intravitreal bevacizumab” or “intravitreal Avastin” combined with “systemic side effects,” “systemic complications,” or “systemic adverse,” or “systemic adverse event.” The search yielded 147 articles published over almost two decades. After screening and assessment, we selected and summarized 40 primary studies that mentioned IVB-related systemic complications.
Conclusions: IVB-induced systemic complications, such as arteriothrombotic events, venous thrombotic events, and hypertension, are rare but potentially serious. Care should be taken when administering multiple doses of intravitreal IVB to patients with pre-existing kidney dysfunction. Bevacizumab-related toxicity must be considered in cases of sudden deterioration of renal function and / or unexpected granulomatous skin lesions in oncologic or chronically polymedicated patients.

Background: Traumatic choroidal rupture is a posterior segment manifestation of trauma and is more common in closed-globe injuries. It is defined as a tear of the choroid and Bruch’s membrane following blunt trauma. This narrative review summarizes the current literature and provides a practical clinical approach to the diagnosis and management of traumatic choroidal rupture and its complications.
Methods: In this narrative review, we searched the PubMed/MEDLINE database using the search term choroidal rupture to provide a practical and updated approach to traumatic choroidal rupture, focusing on its definition, etiology, diagnosis, imaging, management of complications, and prognosis as mentioned in the literature over the last two decades.
Results: Traumatic choroidal rupture occurs due to increased tensile stress on the eye wall and is three-fold more common in closed-globe injuries than in open injuries. Subretinal or sub-retinal pigment epithelial hemorrhage and macular edema are early signs. Macular involvement is associated with poor visual prognosis. Damage to Bruch’s membrane increases the risk of subretinal choroidal neovascular membrane (CNVM). Traumatic epiretinal membrane is another complication. Imaging modalities such as spectral-domain optical coherence tomography, indocyanine green angiography, conventional fundus fluorescein angiography, and optical coherence tomography angiography (OCT-A) can be used in diagnosis or monitoring for complications. OCT-A offers unique opportunities for the diagnosis, treatment, and follow-up of both the initial presentation and possible complications. Frequent follow-up has been suggested in the first year after trauma. Intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection is effective and less invasive in managing CNVM. The visual outcome depends on the location of the rupture, baseline visual acuity, and presence of optic atrophy or macular holes. Risk factors for developing CNVM include rupture involving the macula, longer rupture length or rupture closer to the foveal center, and older age.
Conclusions: Choroidal rupture is a posterior segment entity that usually occurs after trauma, compromises choroidal vessels and Bruch’s membrane, and can lead to CNVM. The use of novel noninvasive imaging modalities and efficient anti-VEGF therapy to manage this entity or its subsequent complications produces better visual outcomes. Early diagnosis and frequent follow-up of these patients allow treatment of possible complications, thereby improving the visual prognosis.

Background: Age-related macular degeneration (AMD) is a major cause of vision loss. Its prevalence has increased over the past decade. This increase is partly due to the scarcity of preventive and therapeutic interventions for this disorder, except when it is in its advanced neovascular form. Discovery of effective treatments for AMD is complicated by the multifactorial pathology of the disorder. Thus, it is difficult to determine which potential disease mechanism to target in order to achieve the greatest clinical benefit.
Hypothesis: Over a decade ago, it was hypothesized that many of the pathologies observed in AMD stem from retinal pigment epithelial (RPE) cell senescence. This provided a potentially key mechanistic target. Supporting this hypothesis, many of the agents that were in development or clinical use for AMD at that time influenced RPE cell senescence, although they were not utilized for this specific effect. The present article re-evaluates this hypothesis by exploring the logical prediction that if RPE cell senescence is a key contributor to AMD, then inhibition of RPE cell senescence is important in the treatment of AMD. If this hypothesis holds true, the inhibition or reversal of RPE cell senescence or its effects should be a common characteristic of new treatments for AMD.
Conclusions: Over the past decade, many agents have been investigated for the treatment of AMD. Although a few were designed to address cell senescence, the majority targeted other potential pathological mechanisms. In support of our original hypothesis, we now present evidence that many of the newer agents investigated for the treatment of AMD, even those that were not meant to reduce cell senescence or its effects, have this function as part of their activity profiles. Further experimental studies or clinical trials exploring the safety and efficacy of inhibiting RPE cell senescence or reversing its effects are needed to pave the way for improved AMD treatment.

Background: The coronavirus disease (COVID-19) vaccines exert ocular adverse effects, including episcleritis, scleritis, anterior and recurrent uveitis, acute macular neuroretinopathy, paracentral acute middle maculopathy, ophthalmic vein thrombosis, Graves’ disease, arteritic anterior ischemic optic neuropathy,  non-arteritic anterior ischemic optic neuropathy, central serous chorioretinopathy, Vogt-Koyanagi-Harada disease, multifocal choroiditis, cranial nerve palsies such as facial or abducens nerve palsy, acute zonal occult outer retinopathy, acute zoster ophthalmicus following re-activation of the varicella-zoster virus, acute retinal necrosis, and multiple evanescent white dot syndrome. In this case report, we explored the possibility of macular branch retinal vein occlusion and its association with COVID-19 vaccination.
Case Presentation: A 44-year-old healthy woman presented with unilateral nonprogressive blurring of vision in the right eye (OD). Her best-corrected distance visual acuity (BCDVA) in OD was 20 / 40. The anterior-segment evaluation was normal. Fundus evaluation of the OD revealed macular branch vein occlusion. She had a history of COVID-19 vaccination within 1 month. The interleukin-6 level was elevated six folds to 30.5 pg / mL. However, COVID-19 immunoglobulin G (IgG) antibodies were negative. Infective etiologies, such as tuberculosis and dengue, were ruled out. Spectral-domain optical coherence tomography (SD-OCT) of the OD showed hyperreflective dots in the posterior vitreous, inner retinal swelling, and cystoid changes in the macula. The maximum central macular thickness was 486 mm. A single dose of bevacizumab was administered at OD intravitreally. At the final follow-up 2.5 months later, her BCDVA had improved to 20 / 20 OD. Fundus evaluation revealed fewer retinal hemorrhages and cotton wool spots. SD-OCT of the OD showed a normal foveal contour and absence of cystoid spaces. Her maximum central macular thickness was 236 mm.
Conclusions: A temporal effect of vein occlusion secondary to COVISHIELD™ vaccination may occur in the absence of systemic risk factors. The interleukin-6 level was elevated, and the remaining blood test results were within normal limits. Since this is a case report, it is limited by the absence of strong evidence to prove this causal relationship between macular branch retinal vein occlusion and the specific brand of COVID-19 vaccination.