Melatonin mitigates disrupted circadian rhythms, lowers intraocular pressure, and improves retinal ganglion cells function in glaucoma.

Glaucoma is a progressive optic neuropathy associated with damage to retinal ganglion cells (RGCs) and disrupted circadian rhythms. Melatonin is a promising substance to ameliorate glaucoma-associated compromised circadian rhythms, sleep, mood, and retinal cells function. However, studies estimating melatonin effects in glaucoma are currently lacking. Therefore, In this study, we investigated the effect of long-term (daily at 10:30 pm for 90 days) oral melatonin administration on systemic (Tb) and local to the organ of vision (IOP) circadian rhythms, pattern electroretinogram (PERG), sleep, and mood, depending on glaucoma stage in patients diagnosed with stable or advanced primary open-angle glaucoma. In a laboratory study in 15 of them, 24-hour records of salivary melatonin were obtained and MTNR1B receptor gene polymorphism was assessed. Melatonin increased the stability of the Tb circadian rhythm by improving its phase alignment and alignment with IOP. Melatonin time-dependently decreased IOP and IOP standard deviation (SD). IOP 24-hour mean and IOP SD decreases were more pronounced in individuals with the higher initial 24-hour IOP mean. Melatonin improved RGCs function in advanced glaucoma; N95 amplitude increase correlated positively with RGCs loss. The beneficial effects of melatonin on sleep and mood were greater in advanced glaucoma. Finally, delayed salivary melatonin and Tb phases were observed in MTNR1B G-allele carriers with advanced glaucoma. Combined, these results provide evidence for melatonin efficiency in restoring disrupted circadian rhythms in glaucoma with different effects of melatonin on systemic vs. local circadian rhythms, indicating that a personalized strategy of melatonin administration may further refine its treatment benefits.

Alternative ways to optimize treatment for retinal vein occlusion with peripheral capillary non-perfusion: a pilot study.

PURPOSE:: We compared the efficacy and safety of ranibizumab versus ranibizumab plus scatter laser photocoagulation (SLP) in patients with chronic post-central retinal vein occlusion (CRVO) macular edema (ME). METHODS:: This prospective non-randomized pilot study included 250 patients with peripheral retinal ischemia and CRVO-related ME. The mean follow-up period was 24.5 ± 6.5 months. The clinical assessments conducted included best corrected visual acuity, optical coherence tomography, and multi-field fluorescein angiography with measurement of the ischemic area. The study population comprised two comparable patient groups with peripheral retinal ischemia that received different treatments for post-CRVO ME: ranibizumab with peripheral SLP of capillary non-perfusion areas (Group 1); and Lucentis® monotherapy (Group 2). Data analyses were performed using Statistica 7 software suite and included the estimation of х ± δ values and their dispersion and covariation coefficients at different stages of the study. RESULTS:: Clinically significant retinal ischemia was detected in 175 (70%) patients, occupying an average of 435.12 ± 225.13 mm2, i.e., 167.15 ± 45.16 optic disc areas. Peripheral ischemia was found in 125 patients, representing 50% of all patients with CRVO and 71.4% of all patients with ischemic CRVO. The mean number of ranibizumab injections in patients who underwent SLP was 3.5 ± 1.6. Patients treated with ranibizumab monotherapy for 24 months received 10.6 ± 2.5 injections. Functional and anatomic results were comparable in the two groups. CONCLUSIONS:: The combination of ranibizumab injections and peripheral SLP in capillary non-perfusion areas can significantly decrease the number of injections and reduce neovascular complications.

Alternative ways to optimize treatment for retinal vein occlusion with peripheral capillary non-perfusion: a pilot study / Opções alternativas para otimizar o tratamento da oclusão da veia retiniana sem perfusão capilar periférica (um estudo piloto)

ABSTRACT Purpose: We compared the efficacy and safety of ranibizumab versus ranibizumab plus scatter laser photocoagulation (SLP) in patients with chronic post-central retinal vein occlusion (CRVO) macular edema (ME). Methods: This prospective non-randomized pilot study included 250 patients with peripheral retinal ischemia and CRVO-related ME. The mean follow-up period was 24.5 ± 6.5 months. The clinical assessments conducted included best corrected visual acuity, optical coherence tomography, and multi-field fluorescein angiography with measurement of the ischemic area. The study population comprised two comparable patient groups with peripheral retinal ischemia that received different treatments for post-CRVO ME: ranibizumab with peripheral SLP of capillary non-perfusion areas (Group 1); and Lucentis® monotherapy (Group 2). Data analyses were performed using Statistica 7 software suite and included the estimation of х ± δ values and their dispersion and covariation coefficients at different stages of the study. Results: Clinically significant retinal ischemia was detected in 175 (70%) patients, occupying an average of 435.12 ± 225.13 mm2, i.e., 167.15 ± 45.16 optic disc areas. Peripheral ischemia was found in 125 patients, representing 50% of all patients with CRVO and 71.4% of all patients with ischemic CRVO. The mean number of ranibizumab injections in patients who underwent SLP was 3.5 ± 1.6. Patients treated with ranibizumab monotherapy for 24 months received 10.6 ± 2.5 injections. Functional and anatomic results were comparable in the two groups. Conclusions: The combination of ranibizumab injections and peripheral SLP in capillary non-perfusion areas can significantly decrease the number of injections and reduce neovascular complications.

RESUMO Objetivo: A investigação centra-se na terapia de edema macular pós-oclusão da veia retiniana central (OVCR) em casos com isquemia retiniana periférica. O objetivo foi comparar a eficácia e a segurança do tratamento com ranibizumab vs ranibizumab + fotocoagulação com laser de dispersão (SLP) em pacientes com edema macular crônico secundário a oclusão da veia retiniana central isquêmica. Métodos: O estudo prospectivo não-randomizado incluiu 250 pacientes com isquemia retiniana periférica e edema macular relacionados a oclusão da veia retiniana central. O tempo médio de seguimento foi de 24,5 ± 6,5 meses. A avaliação clínica incluiu acuidade visual melhor corrigida, tomografia de coerência óptica (OCT) e angiografia por fluoresceína multi-campo com a medição da área de isquemia. A população estudada foi constituída por dois grupos de pacientes comparáveis com o oclusão da veia retiniana central isquêmica, que receberam tratamento diferente. Em nossa prática anterior, utilizamos ranibizumab (Lucentis®) em monoterapia (de acordo com a licença do medicamento) para edema macular pós-oclusão da veia retiniana central com isquemia retiniana periférica (Grupo 2). Mais recentemente, começamos a combinar ranibizumab com SLP periférica de áreas não perfusão capilar (Grupo 1). As análises de dados foram realizadas com o software Statistica 7 e incluíram a estimação dos valores de х ± δ e seus coeficientes de dispersão e covariân cia em diferentes estágios do estudo. Resultados: Identificou-se isquemia retiniana clinicamente significativa em 175 (70%) pacientes, atingindo uma média de 435,12 ± 225,13 mm2, ou seja, 167,15 ± 45,16 áreas de disco óptico. Isquemia periférica foi encontrada em 125 casos, representando 50% de todos os pacientes com oclusão da veia retiniana central e 71,4% de todos os pacientes com oclusão da veia retiniana central isquêmica. O número médio de injeções de rani bizumab em pacientes com SLP foi de 3,5 ± 1,6. Os pacientes tratados com ranibizu mab em monoterapia durante 24 meses receberam 10,6 ± 2,5 injeções. Os resultados funcionais e anatômicos foram comparáveis nos dois grupos. Conclusões: A combinação de injeções de ranibizumab com SLP periférica em áreas de não-perfusão capilar pode diminuir significativamente o número de injeções e reduzir as complicações neovasculares.

Assessment of dry eye signs and symptoms and ocular tolerance of a preservative-free lacrimal substitute (Hylabak®) versus a preserved lacrimal substitute (Systane®) used for 3 months in patients after LASIK.

Laser-assisted in situ keratomileusis (LASIK) is commonly used to correct refractive defects. The procedure frequently results in dry eye symptoms, usually of short but sometimes longer duration. This study was designed to assess dry eye and ocular tolerability after LASIK in patients treated with a preservative-free lacrimal substitute (Hylabak®) or preserved lacrimal substitute (Systane®). In a single-center, investigator-masked, prospective, noninferiority, clinical study, patients undergoing LASIK surgery were randomized to receive Hylabak or Systane eye drops (one drop in each eye four times daily for 3 months). Fluorescein test scores were the primary efficacy variable and were similar on day 1 (mean 0.26 and 0.28 for Hylabak and Systane, respectively). At the final visit (day 84 ± 3) the fluorescein scores had improved to 0.11 and 0.04, respectively. The difference was not significant and thus noninferiority was established. A trend of more rapid improvement in the Hylabak group was evident. Both treatments were well tolerated and there were no serious adverse events, discontinuations for adverse events or other safety-related reasons, and no systemic adverse events. The results suggest that Hylabak is not less effective than Systane in reducing the symptoms of dry eye after LASIK surgery.