Functional Outcomes and Safety Profile of Trans-Foveal Subthreshold Micropulse Laser in Persistent Central Serous Chorioretinopathy.

Our study evaluated visual function changes after subthreshold micropulse laser (SML) treatment in persistent central serous chorioretinopathy (CSC) and SML safety profile. We conducted a prospective study including 31 fovea-involving CSC patients. The natural course was observed for the first 3 months, SML was performed at 3 months, and SML effectiveness was observed at 6 months. At all three clinical visits, optical coherence tomography (OCT), best corrected visual acuity (BCVA), contrast sensitivity (CS) in five spatial frequencies (1.5, 3.0, 6.0, 12.0, and 18.0 cycles per degree (cpd)), microperimetry (MP), and multifocal electroretinography (mfERG) were performed. The SML safety profile was evaluated with functional and morphological parameters. In the cohort of all CSC patients treated with SML, the statistically significant average improvement was observed in BCVA (p = 0.007), CS-1.5 (p = 0.020), CS-3.0 (p = 0.050), CS-12.0 (p < 0.001), CS-18.0 (p = 0.002), CS (CS-A) (p < 0.001), MP in the central ring (MP-C) (p = 0.020), peripheral ring (MP-P) (p = 0.042), and average retinal sensitivity (MP-A) (p = 0.010). After the SML treatment, mean changes in mfERG amplitudes and implicit times in our cohort were not statistically significant. No morphological or functional adverse effects of SML treatment were observed. SML treatment in persistent CSC episodes leads to significant functional improvement and has an excellent safety profile.

Vancomycin-Associated Hemorrhagic Occlusive Retinal Vasculitis: A Case Series and Systematic Review.

This study describes three unilateral cases of hemorrhagic occlusive retinal vasculitis (HORV) after cataract surgery and a review of the literature until February 2022, including 21 articles reporting HORV cases. Altogether, 61 eyes (41 patients) were included. Twenty patients had bilateral and 21 patients had unilateral HORV. Prophylactic vancomycin was given to all patients. Additional vancomycin use was associated with the worst outcome. The mean time to HORV was 9 days post-cataract surgery. In bilateral cases, the median time between surgeries was 7 days. Visual acuity was < 20/400 in 48%, with no light perception in 20%. Neovascular glaucoma developed in 43%. Central macular thickening or hyperreflectivity of the inner retinal layers on optical coherence tomography was associated with worse outcomes. Corticosteroid treatment, early panretinal laser photocoagulation, or anti-vascular endothelial growth factor therapy, and prophylaxis alternative to vancomycin is recommended. [Ophthalmic Surg Lasers Imaging Retina 2022;53:702-712.].

Choroidal thickening with serous retinal detachment in BRAF/MEK inhibitor-induced uveitis: A case report.

BACKGROUND: Immune checkpoint inhibitors have revolutionized the treatment of patients with unresectable metastatic malignant melanoma. In addition to systemic side effects, several usually mild ocular adverse effects have been reported. We report a case of rarely reported vision-threatening bilateral panuveitis with serous retinal detachment, thickened choroid, and chorioretinal folds associated with dabrafenib and trametinib targeted therapy for B-Raf proto-oncogene serine/threonine kinase (BRAF) mutant metastatic cutaneous melanoma. CASE SUMMARY: A 59-year-old female patient with metastatic melanoma treated with dabrafenib and trametinib presented with blurry vision and central scotoma lasting for 3 d in both eyes. Clinical examination and multimodal imaging revealed inflammatory cells in the anterior chamber, mild vitritis, bullous multiple serous retinal detachments, and chorioretinal folds in both eyes. Treatment with dabrafenib and trametinib was suspended, and the patient was treated with topical and intravenous corticosteroids followed by oral corticosteroid treatment with a tapering schedule. One and a half months after the disease onset, ocular morphological and functional improvement was noted. Due to the metastatic melanoma dissemination, BRAF/mitogen-activated protein kinase inhibitors were reintroduced and some mild ocular adverse effects reappeared, which later subsided after receiving oral corticosteroids. CONCLUSION: Patients on combination therapy with dabrafenib and trametinib may rarely develop severe bilateral panuveitis with a good prognosis. Further studies have to establish potential usefulness of ophthalmological examination for asymptomatic patients. Furthermore, appropriate guidelines for managing panuveitis associated with dabrafenib and trametinib should be established.

The Role of ACE, ACE2, and AGTR2 Polymorphisms in COVID-19 Severity and the Presence of COVID-19-Related Retinopathy.

The proposed SARS-CoV-2-induced dysregulation of the renin-angiotensin-aldosterone (RAAS) system results in endothelial dysfunction and microvascular thrombosis. The retinal plexuses contain terminal vessels without anastomotic connections, making the retina especially susceptible to ischemia. This study aimed to determine the role of selected polymorphisms of genes in the RAAS pathway in COVID-19 severity and their association with the presence of COVID-19 retinopathy. 69 hospitalized patients in the acute phase of COVID-19 without known systemic comorbidities and 96 healthy controls were enrolled in this prospective cross-sectional study. The retina was assessed with fundus photography using a Topcon DRI OCT Triton (Topcon Corp., Tokyo, Japan) in the COVID-19 unit. Genotyping of selected polymorphisms in the genes for ACE (rs4646994), ACE2 (rs2285666), and AGTR2 (rs1403543) was performed. The COVID-19 group was divided into mild (n = 12) and severe (n = 57), and then further divided according to the presence of COVID-19 retinopathy (Yes, n = 50; No, n = 19). The presence of the AGTR2 rs1403543-AA genotype was associated with a 3.8-fold increased risk of COVID-19 retinopathy (p = 0.05). The genotype frequencies of selected gene polymorphisms were not significantly associated with either the presence of COVID-19 or its severity. This is the first study demonstrating a borderline association of the AGTR2 rs1403543-AA genotype with COVID-19 retinopathy in males; hence, the AGTR2 rs 1403543 A allele might represent a genetic risk factor for COVID-19 retinopathy in males.

Visual function during and after an acute central serous chorioretinopathy episode.

PURPOSE: To evaluate visual function parameters during and after an acute central serous chorioretinopathy (CSC) episode. METHODS: A prospective study included 19 fovea involving acute CSC patients with episode resolution within 3 months from the episode onset. Optical coherence tomography, best corrected visual acuity (BCVA), contrast sensitivity (CS), microperimetry (MP), and multifocal electroretinography (mfERG) were performed at baseline, 3 and 6 months from the episode onset. In a sub analysis, patients were divided into groups with greater (gMV, N = 9) and lower (lMV, N = 10) macular volume at presentation, and functional outcomes were observed. RESULTS: BCVA (p < 0.001), average CS (CS-A) (p < 0.001), average retinal sensitivity (MP-A) (p < 0.001), mfERG amplitude densities in the first and second ring (mfERG-A1, p < 0.001; mfERG-A2, p = 0.017), and implicit times in the first, second, and third ring (mfERG-IT1, p = 0.024; mfERG-IT2, p = 0.002; mfERG-IT3, p = 0.018) improved with episode resolution 3 months after the episode onset. From 3 to 6 months after the episode onset, only CS-A (p = 0.045) continued to improve. Patients in the gMV group had lower mfERG-A1 (p = 0.017) and central retinal sensitivity (MP-C, p = 0.05) 6 months from the episode onset. CONCLUSIONS: Although all functional parameters mostly improve with CSC episode resolution, only CS continues to improve thereafter. Patients with greater MV at presentation have worse functional outcomes. Visual function impairment in acute CSC patients is confined to the topographical area of subretinal fluid detachment.

Various clinical presentations of uveitis associated with durvalumab treatment.

BACKGROUND: Immune checkpoint inhibitors (ICI) are becoming increasingly common in treating several cancer types. Durvalumab is a human IgG1 monoclonal antibody that blocks PD-L1 binding to PD-1 and CD80 and has recently been approved for the treatment of extensive-stage small-cell lung cancer (ES-SCLC) and locally advanced unresectable (NSCLC). The present review aimed to analyse immune-mediated uveitis, secondary to durvalumab treatment, through a review of the literature and a presentation of two clinical cases. PATIENTS AND METHODS: A literature review using PubMed search was conducted to identify cases of uveitis secondary to durvalumab and cases of uveitis with optic disc oedema secondary to ICI use that were reported prior to November 14, 2021. Additionally, we report two cases of uveitis consequent on durvalumab treatment. RESULTS: Five cases of uveitis secondary to durvalumab use were identified in the literature. Anterior, posterior uveitis and vasculitis were reported. Additionally, we present a case of bilateral intermediate uveitis with bilateral optic disc oedema and a case of bilateral posterior uveitis. Our further search revealed 12 cases of uveitis with optic disc oedema secondary to ICI use, with the majority of cases reported secondary to PD-1 inhibitors. CONCLUSIONS: Rarely reported, uveitis secondary to durvalumab can present various clinical pictures and requires a thorough diagnostic workup. Once the diagnosis is established, treatment, commonly with a local or systemic corticosteroid, should be adapted to the severity of the inflammation.

Associations of Single-Nucleotide Polymorphisms in Slovenian Patients with Acute Central Serous Chorioretinopathy.

Central serous chorioretinopathy (CSC) is a chorioretinal disease that usually affects the middle-aged population and is characterised by a thickened choroid, retinal pigment epithelium detachment, and subretinal fluid with a tendency towards spontaneous resolution. We investigated 13 single-nucleotide polymorphisms (SNPs) in 50 Slovenian acute CSC patients and 71 healthy controls in Complement Factor H (CFH), Nuclear Receptor Subfamily 3 Group C Member 2 (NR3C2), Cadherin 5 (CDH5) Age-Related Maculopathy Susceptibility 2 (ARMS2), TNF Receptor Superfamily Member 10a (TNFRSF10A), collagen IV alpha 3 (COL4A3) and collagen IV alpha 4 (COL4A4) genes using high-resolution melt analysis. Statistical calculations revealed significant differences in genotype frequencies for CFH rs1329428 (p = 0.042) between investigated groups and an increased risk for CSC in patients with TC (p = 0.040) and TT (p = 0.034) genotype. Genotype-phenotype correlation analysis revealed that CSC patients with CC genotype in CFH rs3753394 showed a higher tendency for spontaneous CSC episode resolution at 3 months from the disease onset (p = 0.0078), which could indicate clinical significance of SNP testing in CSC patients. Bioinformatics analysis of the non-coding polymorphisms showed alterations in transcription factor binding motifs for CFH rs3753394, CDH5 rs7499886 and TNFRSF10A rs13278062. No association of collagen IV polymorphisms with CSC was found in this study.

Do females and males exhibit a similar sarcopenic response as a consequence of normoxic and hypoxic bed rest?

NEW FINDINGS: What is the central question of this study? Do females and males exhibit a similar sarcopenic response as a consequence of normoxic and hypoxic bed rest? What is the main finding and its importance? During 10-day bed rest, exposure to a simulated (normobaric hypoxia) altitude of ∼4000 m does not exert additional significant structural or functional effect on the weight-bearing muscles in females compared to those noted under normoxic conditions. Whereas males and females exhibit decrements in muscle cross-sectional area and mass during normoxic and hypoxic bed rest, a concomitant strength decrement was only observed in males. ABSTRACT: This study investigated the effects of hypoxia on the known processes of adaptation of body composition and muscle function to normoxic inactivity. Females (n = 12) and males (n = 11) took part in the following interventions: hypoxic ambulation (HAMB; ∼4000 m); hypoxic bed rest (HBR; ∼4000 m) and normoxic bed rest (NBR). Prior to and immediately following each intervention, body composition, thigh and lower leg cross-sectional area (CSA) and isometric muscular strength were recorded. Participants lost body mass (HAMB: male -1.5 ± 0.9 kg, female -1.9 ± 0.7 kg; HBR: male -2.0 ± 1.8 kg, female -2.4 ± 0.8 kg; NBR: male -1.4 ± 1.3 kg, female -1.4 ± 0.9 kg) and lean mass (HAMB: male -3.9 ± 3.0%, female -3.4 ± 2.0%; HBR: male -4.0 ± 4.4%, female -4.1 ± 2.0%; NBR: male -4.0 ± 3.4%, female -2.2 ± 2.7%) with no between-condition or sex differences. Knee extension decreased for males in NBR compared to HAMB (HAMB: male -0.2 ± 9.1%, female 1.3 ± 4.9%; HBR: male -7.8 ± 10.3%, female -3.3 ± 10.9%; NBR: male -14.5 ± 11%, female -3.4 ± 6.9%). Loss of force during maximal voluntary contraction (MVC) in the knee extensors was significantly different between males and females following NBR. There were no other significant changes noted following the experimental interventions. There were no differences recorded between sexes in maximal MVC for elbow or ankle joints. Female lower leg CSA decreased following bed rest (HAMB: -4.5 ± 2.0%; HBR: -9.9 ± 2.6%; NBR: -8.0 ± 1.6%). These findings indicate that a 10-day hypoxic bed rest does not exert any significant additional effect on muscle atrophy when compared to NBR, except for female thigh CSA. In contrast to males, who exhibited a significant loss of muscle strength, no such decrement in strength was observed in the female participants.

Ski-Everest (8848 m) Expedition: Digit Skin Temperature Responses to Cold Immersion May Reflect Susceptibility to Cold Injury.

INTRODUCTION: We tested the hypothesis that individual susceptibility to freezing cold injury might be reflected in an attenuated cold-induced vasodilatation (CIVD) response by comparing the CIVD responses of an elite alpinist with a history of freezing cold injury in the feet (case alpinist) with those of an age- and ability- matched noninjured alpinists control group (controls). According to this hypothesis, the vasomotor responses to a CIVD test of the case alpinist would represent a pathophysiological response when compared with the normal physiological response of a noninjured cohort. METHODS: The case alpinist and the controls in the cohort group conducted a cold water immersion test comprising sequential immersion of a hand and foot for 5 min in 35°C water, followed by a 30-min immersion in 8°C water and a 10-min recovery period in room air. During this test we monitored the finger and toe skin temperatures. RESULTS: The case alpinist had a significantly attenuated CIVD response and a lower skin temperature in all injured and noninjured digits during immersion (∼2°C lower than in the control group) and an attenuated recovery of finger skin temperatures (∼6°C lower than in the control group). CONCLUSIONS: The attenuated CIVD response of the case alpinist may reflect a previously unrecognized enhanced susceptibility to frostbite. In addition to the poor vasomotor response observed in the injured toes, he also exhibited a poor vasomotor response in his noninjured fingers. The results of the present study indicate that a test of vasomotor activity during thermal stress may identify individuals predisposed to cold injury.

Ocular Changes in Metastatic Melanoma Patients Treated with MEK Inhibitor Cobimetinib and BRAF Inhibitor Vemurafenib.

BACKGROUND: Mitogen-activated protein kinase kinase (MEK) inhibitor cobimetinib and V-raf murine sarcoma viral oncogene homolog B1 (BRAF) inhibitor vemurafenib have significantly improved the prognosis of BRAF-mutated metastatic melanoma. Some ocular symptoms and signs were recently recognized to follow this treatment. The study was aimed to investigate ocular toxicity in patients with metastatic melanoma treated with cobimetinib in combination with vemurafenib. PATIENTS AND METHODS: In the prospective, observational study, patients with BRAF-mutated metastatic melanoma treated with cobimetinib in combination with vemurafenib at the Institute of Oncology Ljubljana were asked to participate. Ophthalmic examination was performed including measurement of visual acuity and intraocular pressure, slit lamp examination, funduscopy (CF), infrared-reflectance (IR) imaging and optical coherence tomography (OCT). RESULTS: Five out of 7 patients noticed changes in vision few days after starting the therapy with cobimetinib. In all patients, small circular lesions, described as MEKAR lesions, were documented in outer retinal layers demonstrated with OCT, IR, and CF. Changes were in the center and/or scattered over the retina almost symmetrical in both eyes in 6 patients, and asymmetrical in one patient, the latter presented also with unilateral anterior uveitis and cystoid macular edema. CONCLUSIONS: Multiple bilateral foveal and extrafoveal small retinal lesions in the outer retinal layers develop in patients treated with MEK inhibitor in combination with BRAF inhibitor. Ophthalmologists and oncologists need to be aware of this common, yet relatively benign and often transient ocular side effect to avoid needless intervention, including the discontinuance of a potentially life-prolonging therapy.

Factors influencing the success of radioiodine therapy in patients with Graves' disease.

OBJECTIVE: The first dose of radioiodine (I) does not always cure hyperthyroidism in patients with Graves' disease (GD). Our aim was to evaluate the factors influencing the success of I therapy. PATIENTS AND METHODS: We reviewed the medical records of 724 patients who were first diagnosed with GD between 2005 and 2009 and were subsequently treated with I in a fixed-dose manner considering the thyroid volume (TV). TSH, fT(4), and fT(3) were measured. TV was measured by means of ultrasonography. Successful therapy was followed by euthyroidism or hypothyroidism. RESULTS: Out of 724 patients, 656 (90.5%) were successfully (Group 1) and 69 (9.5%) were unsuccessfully (Group 2) treated with the first dose of (131)I. In Group 1, the applied dose of (131)I was lower than that in Group 2 [626±107, 95% confidence interval (CI) 618-634, and 709±140, 95% CI 675-742 MBq, respectively; P<0.001]. At presentation, patients in Group 1 were younger than those in Group 2 (45.5±14.9, 95% CI 44.4-46.6, and 50.1±15.8, 95% CI 46.3-53.9 years, respectively; P=0.031). They had a lower fT(4) (54.9±26.1, 95% CI 52.9-56.9, and 72.1±34.1, 95% CI 63.9-80.3 pmol/l, respectively; P<0.001), a lower fT3 (20.9±8.2, 95% CI 20.3-21.5, and 23.9±8.2, 95% CI 21.9-25.9 pmol/l, respectively; P<0.001), and a smaller TV (21.5±13.2, 95% CI 20.2-22.8, and 35.6±22.3, 95% CI 28.2-42.9 ml, respectively; P<0.001). Before I therapy, patients in Group 1 had a lower fT(3) (9.6±6.0, 95% CI 9.2-10.1, and 11.3±7.6, 95% CI 9.5-13.2 pmol/l, respectively; P=0.038). CONCLUSION: Successfully treated GD patients were younger, less severely hyperthyroid, and had a smaller TV at presentation. They were also less severely hyperthyroid before I therapy.

Circadian rhythm of peripheral perfusion during 10-day hypoxic confinement and bed rest.

INTRODUCTION: Future planetary habitats will be hypobaric and hypoxic to reduce the risk of decompression sickness during preparation for extra-vehicular activities. This study was part of a research programme investigating the combined effects of hypoxia and microgravity on physiological systems. PURPOSE: We tested the hypothesis that hypoxia-induced peripheral vasoconstriction persists at night and is aggravated by bed rest. Since sleep onset has been causally linked to nocturnal vasodilatation, we reasoned that hypoxia-induced vasoconstriction at night may explain sleep disturbances at altitude. Peripheral perfusion alterations as a consequence of bed rest may explain poor sleep quality reported during sojourns on the International Space Station. METHODS: Eleven males underwent three 10-day interventions in a randomised order: (1) hypoxic ambulatory confinement; (2) hypoxic bed rest; (3) normoxic bed rest. During each intervention we conducted 22-h monitoring of peripheral perfusion, as reflected by the skin temperature gradient. Measurements were conducted on the first (D 1) and last day (D 10) of each intervention. RESULTS: All interventions resulted in a decrease in daytime toe perfusion from D 1 to D 10. There was no difference in the magnitude of the daytime reduction in toe perfusion between the three interventions. There was a significant vasodilatation of the toes in all interventions by 11 pm. The fingertips remained well perfused throughout. CONCLUSIONS: Daytime vasoconstriction induced by hypoxia and/or bed rest is abolished at night, lending further support to the theory that changes in peripheral skin temperature may be functionally linked to sleep onset.

Efficacy of 12-month treatment of neovascular age-related macular degeneration with intravitreal bevacizumab based on individually determined injection strategies after three consecutive monthly injections.

PURPOSE: To report the results of intravitreal treatment with bevacizumab in neovascular age-related macular degeneration (AMD) after a loading dose (LD) of three monthly injections followed by an optical coherence tomography (OCT)-guided strategy, based on best-corrected visual acuity (VA) and number of injections required over 1 year. METHODS: A series of consecutive cases of 149 eyes of 147 patients received three or more intravitreal injections of bevacizumab (1.25 mg) for neovascular AMD over a 1-year period. The patients underwent ophthalmological examinations: measurement of the VA, fluorescein angiography, dilated fundus examination at baseline; VA, OCT and dilated fundus examination at monthly follow-up visits. Repeated injections were given each month for the first 3 months (LD); thereafter, injections were only administered if leakage or macular oedema were present. RESULTS: Mean baseline VA was 51 ± 14 letters, which improved to 58 ± 15 letters (p < 0.0001; n = 149) at first evaluation (15 ± 2 weeks), 59 ± 15 letters (p < 0.0001; n = 143) at second evaluation (25 ± 2 weeks) and 57 ± 16 letters (p < 0.0001; n = 132) at third evaluation (51 ± 3 weeks). The baseline mean central retinal thickness (344.6 µm) and total macular volume (8.6 mm(3) ) decreased at first evaluation, to 219.0 µm (p < 0.0001) and 7.2 mm(3) (p < 0.0001), respectively. The mean number of injections per patient treated for 1 year was 5.1 (range 3-9). No systemic side-effects were noted. CONCLUSION: Treatment of neovascular AMD with intravitreal bevacizumab administered in LD of three monthly injections and followed by an OCT-guided strategy provides functional and anatomical improvements for up to 1 year.

Decompression-induced ocular tear film bubbles reflect the process of denitrogenation.

PURPOSE: To confirm that the tear film bubbles observed after decompression from hyperbaric exposure are due to denitrogenation and to assess the time course of denitrogenation based on the number of ocular tear film bubbles. METHODS: The study comprised two parts. In the first, subjects (n = 8) were compressed to a pressure of 2.0 ATA (atmospheres absolute; depth of 10 meters of sea water [msw]) for 60 minutes in a hyperbaric chamber on two separate occasions. On one occasion they breathed air, whereas on the second occasion they inspired pure oxygen. Before and within 30 minutes after each dive, the subjects' tear film was examined with a slit lamp microscope and the average number of bubbles recorded. Ultrasound reflectivity of the lens-vitreous humor compartments was also examined. In the second part of the study, subjects (n = 8) participated in two simulated dives in the hyperbaric chamber: 4.0 ATA (30 msw) for 15 minutes and 2.5 ATA (15 msw) for 180 minutes. The former was a no-stop decompression dive, whereas the latter required a 43-minute decompression stop at 3 msw. Ocular tear film examinations were conducted before the dive, as well as 30 minutes and 1 day, 2 days, and 3 days after the dives. RESULTS: The number of tear film bubbles increased significantly (P < 0.05) after the air dives to 2.0 ATA for 60 minutes, whereas there was no significant postdecompression increase in tear film when oxygen was inspired by the subjects during the dive. Posterior lens-vitreous humor reflectivity increased significantly after decompression from 2 ATA, when air was the breathing mixture, whereas no change in reflectivity was observed when oxygen was inspired during the dive. In the second part of the study, there was a significant elevation in tear film bubbles for 2 days after the two dives (P < 0.05). There was no significant difference in the number of ocular tear film bubbles between the two dives. CONCLUSIONS: After a hyperbaric air exposure, tear film bubbles reflect the process of denitrogenation, which may persist for up to 2 days after the decompression.

Visual function after prolonged bed rest.

The present study evaluated the claim of earlier reports, that of bed rest-induced alterations in visual function. Indices of visual function were studied in 10 healthy male subjects, during 35 days of horizontal bed rest. Before and after the 35 day bed rest, both eyes of all subjects were examined for visual acuity, intraocular pressure, contrast sensitivity, stereopsis and visual field. Pre- and post-bed rest values were compared with Student's T-test. There were no significant differences in any of the measured indices of visual function.