Cardiac Screening and Disease Characteristics of Patients with Ocular Sarcoidosis.

PURPOSE: This is a retrospective nonrandomized cohort study investigating the prevalence, timing, and type of cardiac sarcoidosis indications on electrocardiogram in patients with diagnosed or suspected ocular sarcoidosis. METHODS: Medical histories of individuals seen from 2005 to 2020 at two centers with diagnosed or suspected ocular sarcoidosis were searched, and statistical methods were used to evaluate the relevance of each aspect obtained. RESULTS: Approximately 16% of the individuals in our cohort showed signs of cardiac sarcoidosis on ECG, primarily bundle branch blocks, and premature ventricular contractions, close to the time of their initial ocular sarcoidosis documentation. Males exhibited higher rates of clinically significant extra-pulmonary sarcoidosis. No other demographic differences were found. CONCLUSIONS: Our findings highlight the importance for further differentiation of non-infectious sarcoidosis and the utility of electrocardiogram screening. Studies with larger cohorts of ocular sarcoidosis might be needed to elucidate demographic differences within this patient population.

The Risk of Postoperative Complications After Major Elective Surgery in Active or Resolved COVID-19 in the United States.

OBJECTIVE: To assess the association between the timing of surgery relative to the development of Covid-19 and the risks of postoperative complications. SUMMARY BACKGROUND DATA: It is unknown whether patients who recovered from Covid-19 and then underwent a major elective operation have an increased risk of developing postoperative complications. METHODS: The risk of postoperative complications for patients with Covid-19 undergoing 18 major types of elective operations in the Covid-19 Research Database was evaluated using multivariable logistic regression. Patients were grouped by time of surgery relative to SARS-CoV-2 infection; that is, surgery performed: (1) before January 1, 2020 ("pre-Covid-19"), (2) 0 to 4 weeks after SARS-CoV-2 infection ("peri-Covid-19"), (3) 4 to 8 weeks after infection ("early post-Covid-19"), and (4) ≥8 weeks after infection ("late post-Covid-19"). RESULTS: Of the 5479 patients who met study criteria, patients with peri-Covid-19 had an elevated risk of developing postoperative pneumonia [adjusted odds ratio (aOR), 6.46; 95% confidence interval (CI): 4.06-10.27], respiratory failure (aOR, 3.36; 95% CI: 2.22-5.10), pulmonary embolism (aOR, 2.73; 95% CI: 1.35-5.53), and sepsis (aOR, 3.67; 95% CI: 2.18-6.16) when compared to pre-Covid-19 patients. Early post-Covid-19 patients had an increased risk of developing postoperative pneumonia when compared to pre-Covid-19 patients (aOR, 2.44; 95% CI: 1.20-4.96). Late post-Covid-19 patients did not have an increased risk of postoperative complications when compared to pre-Covid-19 patients. CONCLUSIONS: Major, elective surgery 0 to 4 weeks after SARS-CoV-2 infection is associated with an increased risk of postoperative complications. Surgery performed 4 to 8 weeks after SARS-CoV-2 infection is still associated with an increased risk of postoperative pneumonia, whereas surgery 8 weeks after Covid-19 diagnosis is not associated with increased complications.

Sustained Inhibition of NF-κB Activity Mitigates Retinal Vasculopathy in Diabetes.

This study investigated the effects of long-term NF-κB inhibition in mitigating retinal vasculopathy in a type 1 diabetic mouse model (Akita, Ins2Akita). Akita and wild-type (C57BL/6J) male mice, 24 to 26 weeks old, were treated with or without a selective inhibitor of NF-κB, 4-methyl-N1-(3-phenyl-propyl) benzene-1,2-diamine (JSH-23), for 4 weeks. Treatment was given when the mice were at least 24 weeks old. Metabolic parameters, key inflammatory mediators, blood-retinal barrier junction molecules, retinal structure, and function were measured. JSH-23 significantly lowered basal glucose levels and intraocular pressure in Akita. It also mitigated vascular remodeling and microaneurysms significantly. Optical coherence tomography of untreated Akita showed thinning of retinal layers; however, treatment with JSH-23 could prevent it. Electroretinogram demonstrated that A- and B-waves in Akita were significantly smaller than in wild type mice, indicating that JSH-23 intervention prevented loss of retinal function. Protein levels and gene expression of key inflammatory mediators, such as NOD-like receptor family pyrin domain-containing 3, intercellular adhesion molecule-1, inducible nitric oxide synthase, and cyclooxygenase-2, were decreased after JSH-23 treatment. At the same time, connexin-43 and occludin were maintained. Vision-guided behavior also improved significantly. The results show that reducing inflammation could protect the diabetic retina and its vasculature. Findings appear to have broader implications in treating not only ocular conditions but also other vasculopathies.

Clinical, radiographic, and intraoperative risk factors for retinal detachment after open globe injury.

PURPOSE: Retinal detachment (RD) is a vision-threatening complication of open globe injuries (OGI). This study sought to assess clinical, radiographic, and intraoperative risk factors for RD after OGI. A secondary goal was to test the retinal detachment after open globe injury (RD-OGI) score. METHODS: Records of patients undergoing OGI repair at a single trauma center over 3 years were reviewed using a retrospective case series design. Eyes that were enucleated or lost to follow up within 30 days of OGI without evidence of RD were excluded. Potential risk factors for RD development were assessed by logistic regression or chi-square tests were appropriate and were entered into a multivariate logistic regression if significant on univariate analysis. Risk of RD for each eye was categorized by its RD-OGI score. RESULTS: Seventy-three eyes (72 patients) were included. In univariate analysis, afferent pupillary defect, worse visual acuity, posterior injury, vitreous hemorrhage, and posterior segment volume loss (PSVL) on CT were strong predictors of RD. In multivariate analysis, only PSVL on CT (adjusted OR 10.8, P = 0.025) maintained a statistically significant association with RD risk. At 1 year, 5% of low-risk eyes, 20% of moderate-risk eyes, and 67% of high-risk eyes developed RD. These rates were not significantly different from the RD-OGI derivation or validation cohorts (P = 0.90 and P = 0.67, respectively). CONCLUSION: PSVL on CT increases the risk of RD after OGI. The RD-OGI Score was a good prognostic tool for assessing RD risk after OGI in this population.

Hydrogen sulfide intervention in cystathionine-ß-synthase mutant mouse helps restore ocular homeostasis.

AIM: To investigate the applications of hydrogen sulfide (H2S) in eye-specific ailments in mice. METHODS: Heterozygous cystathionine-ß-synthase (CBS+/-) and wild-type C57BL/6J (WT) mice fed with or without high methionine diet (HMD) were administered either phosphate buffered saline (PBS) or the slow-release H2S donor: GYY4137. Several analyses were performed to study GYY4137 effects by examining retinal lysates for key protein expressions along with plasma glutamate and glutathione estimations. Intraocular pressure (IOP) was monitored during GYY4137 treatment; barium sulfate and bovine serum albumin conjugated fluorescein isothiocyanate (BSA-FITC) angiographies were performed for examining vasculature and its permeability post-treatment. Vision-guided behavior was also tested employing novel object recognition test (NORT) and light-dark box test (LDBT) recordings. RESULTS: CBS deficiency (CBS+/-) coupled with HMD led disruption of methionine/homocysteine (Hcy) metabolism leading to hyperhomocysteinemia (HHcy) in CBS+/- mice as reflected by increased Hcy, and s-adenosylhomocysteine hydrolase (SAHH) levels. Unlike CBS, cystathionine-γ lyase (CSE), methylenetetrahydrofolate reductase (MTHFR) levels which were reduced but compensated by GYY4137 intervention. Heightened oxidative and endoplasmic reticulum (ER) stress responses were mitigated by GYY4137 effects along with enhanced glutathione (GSH) levels. Increased glutamate levels in CBS+/- strain were prominent than WT mice and these mice also exhibited higher IOP that was lowered by GYY4137 treatment. CBS deficiency also resulted in vision-guided behavioral impairment as revealed by NORT and LDBT findings. Interestingly, GYY4137 was able to improve CBS+/- mice behavior together with lowering their glutamate levels. Blood-retinal barrier (BRB) appeared compromised in CBS+/- with vessels' leakage that was mitigated in GYY4137 treated group. This corroborated the results for occludin (an integral plasma membrane protein of the cellular tight junctions) stabilization. CONCLUSION: Findings reveal that HHcy-induced glutamate excitotoxicity, oxidative damage, ER-stress and vascular permeability alone or together can compromise ocular health and that GYY4137 could serve as a potential therapeutic agent for treating HHcy induced ocular disorders.

Evaluation of focal damage in the retinal pigment epithelium layer in serous retinal pigment epithelium detachment.

The purpose of this study was to evaluate focal damage in the retinal pigment epithelium (RPE) layer in serous retinal pigment epithelium detachment (PED) with multi-contrast optical coherence tomography (OCT), which is capable of simultaneous measurement of OCT angiography, polarization-sensitive OCT and standard OCT images. We evaluated 37 eyes with age-related macular degeneration that had serous PED. Focal RPE damage was indicated by hyper-transmission beneath the RPE-Bruch's membrane band in standard OCT images. Distribution of RPE melanin was calculated using the dataset from multi-contrast OCT. Twenty-four points with hyper-transmission were detected in 21 of the 37 eyes. Standard OCT images failed to show disruption of the RPE-Bruch's membrane band at 5 of the 24 hyper-transmission points. Conversely, multi-contrast OCT images clearly showed melanin defects in the RPE-Bruch's membrane band at all points. Areas of melanin defects with disruption of the RPE-Bruch's membrane band were significantly larger than those without disruption. The volume of intraretinal hyper-reflective foci was significantly larger in eyes with hyper-transmission than that in eyes without hyper-transmission. Multi-contrast OCT is more sensitive than standard OCT for displaying changes at the RPE-Bruch's membrane band when there are small areas of RPE damage.

FREQUENT SUBCLINICAL MACULAR CHANGES IN COMBINED BRAF/MEK INHIBITION WITH HIGH-DOSE HYDROXYCHLOROQUINE AS TREATMENT FOR ADVANCED METASTATIC BRAF MUTANT MELANOMA: Preliminary Results From a Phase I/II Clinical Treatment Trial.

PURPOSE: To assess the potential ocular toxicity of a combined BRAF inhibition (BRAFi) + MEK inhibition (MEKi) + hydroxychloroquine (HCQ) regime used to treat metastatic BRAF mutant melanoma. METHODS: Patients with stage IV metastatic melanoma and BRAF V600E mutations (n = 11, 31-68 years of age) were included. Treatment was with oral dabrafenib, 150 mg bid, trametinib, 2 mg/day, and HCQ, 400 mg to 600 mg bid. An ophthalmic examination, spectral domain optical coherence tomography, near-infrared and short-wavelength fundus autofluorescence, and static perimetry were performed at baseline, 1 month, and q/6 months after treatment. RESULTS: There were no clinically significant ocular events; there was no ocular inflammation. The only medication-related change was a separation of the photoreceptor outer segment tip from the apical retinal pigment epithelium that could be traced from the fovea to the perifoveal retina noted in 9/11 (82%) of the patients. There were no changes in retinal pigment epithelium melanization or lipofuscin content by near-infrared fundus autofluorescence and short-wavelength fundus autofluorescence, respectively. There were no inner retinal or outer nuclear layer changes. Visual acuities and sensitivities were unchanged. CONCLUSION: BRAFi (trametinib) + MEKi (dabrafenib) + HCQ causes very frequent, subclinical separation of the photoreceptor outer segment from the apical retinal pigment epithelium without inner retinal changes or signs of inflammation. The changes suggest interference with the maintenance of the outer retinal barrier and/or phagocytic/pump functions of the retinal pigment epithelium by effective MEK inhibition.

ACUTE EXUDATIVE PARANEOPLASTIC POLYMORPHOUS VITELLIFORM MACULOPATHY DURING VEMURAFENIB AND PEMBROLIZUMAB TREATMENT FOR METASTATIC MELANOMA.

PURPOSE: To describe a patient with BRAF mutation-positive cutaneous melanoma who developed acute exudative polymorphous vitelliform maculopathy during vemurafenib and pembrolizumab treatment for metastatic melanoma. METHODS: Retrospective case report documented with wide-field fundus imaging, spectral domain optical coherence tomography, and fundus autofluorescence imaging. RESULTS: A 55-year-old woman with bilateral ductal breast carcinoma and BRAF mutation-positive metastatic cutaneous melanoma complained of bilateral blurred vision within 5 days of starting vemurafenib (BRAF inhibitor). She had been on pembrolizumab (program death receptor antibody) and intermittently on dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor), and had a normal ophthalmologic examination. On presentation three weeks after the introduction of vemurafenib, her visual acuity had declined to 20/40 in both eyes. Her examination showed diffuse elevation of the fovea with multifocal yellow-white, crescent-shaped subretinal deposits within the macula of both eyes and bilateral neurosensory retinal detachments by spectral domain optical coherence tomography. Discontinuation of vemurafenib and introduction of difluprednate and dorzolamide led to a gradual resolution (over four months) of the neurosensory detachments with recovery of vision. CONCLUSION: This case report suggests that acute exudative polymorphous vitelliform maculopathy may be directly associated with the use of BRAF inhibitors as treatment for metastatic cutaneous melanoma, or indirectly by triggering autoimmune-paraneoplastic processes. Future identification of similar associations is required to unequivocally link vemurafenib and/or pembrolizumab to acute exudative polymorphous vitelliform maculopathy in metastatic melanoma.

Circular RNAs constitute an inherent gene regulatory axis in the mammalian eye and brain 1.

Circular RNAs (circRNAs) are being hailed as a newly rediscovered class of covalently closed transcripts that are produced via alternative, noncanonical pre-mRNA back-splicing events. These single-stranded RNA molecules have been identified in organisms ranging from the worm (Cortés-López et al. 2018. BMC Genomics, 19: 8; Ivanov et al. 2015. Cell Rep. 10: 170-177) to higher eukaryotes (Yang et al. 2017. Cell Res. 27: 626-641) to plants (Li et al. 2017. Biochem. Biophys. Res. Commun. 488: 382-386). At present, research on circRNAs is an active area because of their diverse roles in development, health, and diseases. Partly because their circularity makes them resistant to degradation, they hold great promise as unique biomarkers for ocular and central nervous system (CNS) disorders. We believe that further work on their applications could help in developing them as "first-in-class" diagnostics, therapeutics, and prognostic targets for numerous eye conditions. Interestingly, many circRNAs play key roles in transcriptional regulation by acting as miRNAs sponges, meaning that they serve as master regulators of RNA and protein expression. Since the retina is an extension of the brain and is part of the CNS, we highlight the current state of circRNA biogenesis, properties, and function and we review the crucial roles that they play in the eye and the brain. We also discuss their regulatory roles as miRNA sponges, regulation of their parental genes or linear mRNAs, translation into micropeptides or proteins, and responses to cellular stress. We posit that future advances will provide newer insights into the fields of RNA metabolism in general and diseases of the aging eye and brain in particular. Furthermore, in keeping pace with the rapidly evolving discipline of RNA"omics"-centered metabolism and to achieve uniformity among researchers, we recently introduced the term "cromics" (circular ribonucleic acids based omics) (Singh et al. 2018. Exp. Eye Res. 174: 80-92).

Expression Analysis of the Circular RNA Molecules in the Human Retinal Cells Treated with Homocysteine.

PURPOSE: To characterize the global profile of circular RNAs (circRNAs) and their differential expression levels in homocysteine (Hcy)-treated ARPE-19 cells, a line of human retinal pigment epithelial (RPE) cells. MATERIALS AND METHODS: We treated ARPE-19 cells with and without Hcy to investigate the influence of Hcy on circRNA expression levels using dedicated human circRNA microarrays. RESULTS: A total of 12,233 circRNAs were identified out of them 54 were differentially expressed (17 were down-regulated, and 37 were up-regulated) with a fold change >2.0 (p < 0.05) in Hcy-treated versus untreated cells. CONCLUSIONS: To our knowledge, this is the first report profiling circRNAs in human RPE cells post-Hcy treatment mimicking hyperhomocysteinemic (HHcy) conditions that negatively affect retinal biology and vision. These findings are of potential clinical significance as they will help understand Hcy metabolism and HHcy-mediated diseases and identify potential diagnostic and therapeutic targets for eye diseases that are caused by elevated Hcy concentrations.

Remodeling of Retinal Architecture in Diabetic Retinopathy: Disruption of Ocular Physiology and Visual Functions by Inflammatory Gene Products and Pyroptosis.

Diabetic patients suffer from a host of physiological abnormalities beyond just those of glucose metabolism. These abnormalities often lead to systemic inflammation via modulation of several inflammation-related genes, their respective gene products, homocysteine metabolism, and pyroptosis. The very nature of this homeostatic disruption re-sets the overall physiology of diabetics via upregulation of immune responses, enhanced retinal neovascularization, upregulation of epigenetic events, and disturbances in cells' redox regulatory system. This altered pathophysiological milieu can lead to the development of diabetic retinopathy (DR), a debilitating vision-threatening eye condition with microvascular complications. DR is the most prevalent cause of irreversible blindness in the working-age adults throughout the world as it can lead to severe structural and functional remodeling of the retina, decreasing vision and thus diminishing the quality of life. In this manuscript, we attempt to summarize recent developments and new insights to explore the very nature of this intertwined crosstalk between components of the immune system and their metabolic orchestrations to elucidate the pathophysiology of DR. Understanding the multifaceted nature of the cellular and molecular factors that are involved in DR could reveal new targets for effective diagnostics, therapeutics, prognostics, preventive tools, and finally strategies to combat the development and progression of DR in susceptible subjects.

Systemic immunosuppression and risk of age-related macular degeneration.

A local immune response has been implicated in the pathogenesis of age-related macular degeneration (AMD), but it is unclear if systemic immunosuppressive/immunomodulatory therapy (IMT) protects against the onset and/or progression of AMD. We performed a retrospective cohort study using a Cox proportional hazards model of two cohorts. Cohort 1 included patients with stage V chronic kidney disease (CKD) status post kidney transplantation, on at least one IMT agent, and older than 50. Cohort 2 included patients with stage IV or V CKD who had not undergone kidney transplantation, were not on IMT, and were older than 50. The main outcomes were hazard ratios of a new diagnosis of dry AMD, wet AMD, or conversion from dry to wet. There were 10,813 patients in cohort 1, and 217,081 patients in cohort 2. After controlling for sex and age, there was no significant difference in the hazard of developing a new diagnosis of dry AMD (HR = 0.95, 95% CI 0.87-1.05, p = 0.32), developing a new diagnosis of wet AMD without any prior diagnosis of dry AMD (HR = 0.85, 95% CI 0.66-1.08, p = 0.18), or converting from dry to wet AMD (HR 1.24, 95% CI 0.94-1.62, p = 0.12). For patients over 70 on mycophenolate mofetil, there was a reduced hazard of converting from dry to wet AMD (HR = 0.92, 95% CI = 0.85-0.99, p = 0.02). In contrast, everolimus had an increased hazard of dry AMD (HR = 2.14, 95% CI 1.24-3.69, p < 0.01). Most systemic IMT does not affect the risk of onset or progression of AMD in patients with CKD. However, mycophenolate mofetil may confer some degree of protection against the conversion of dry AMD to wet AMD, suggesting that modulation of the immune response may prevent progression of the disease.

A hypothesis for treating inflammation and oxidative stress with hydrogen sulfide during age-related macular degeneration.

Age-related macular degeneration (AMD) is a leading cause of blindness and is becoming a global crisis since affected people will increase to 288 million by 2040. Genetics, age, diabetes, gender, obesity, hypertension, race, hyperopia, iris-color, smoking, sun-light and pyroptosis have varying roles in AMD, but oxidative stress-induced inflammation remains a significant driver of pathobiology. Eye is a unique organ as it contains a remarkable oxygen-gradient that generates reactive oxygen species (ROS) which upregulates inflammatory pathways. ROS becomes a source of functional and morphological impairments in retinal pigment epithelium (RPE), endothelial cells and retinal ganglion cells. Reports demonstrated that hydrogen sulfide (H2S) acts as a signaling molecule and that it may treat ailments. Therefore, we propose a novel hypothesis that H2S may restore homeostasis in the eyes thereby reducing damage caused by oxidative injury and inflammation. Since H2S has been shown to be a powerful antioxidant because of its free-radicals' inhibition properties in addition to its beneficial effects in age-related conditions, therefore, patients may benefit from H2S salubrious effects not only by minimizing their oxidant and inflammatory injuries to retina but also by lowering retinal glutamate excitotoxicity.

Circular RNAs profiling in the cystathionine-ß-synthase mutant mouse reveals novel gene targets for hyperhomocysteinemia induced ocular disorders.

Cystathionine-ß-synthase (CBS) gene encodes L-serine hydrolyase which catalyzes ß-reaction to condense serine with homocysteine (Hcy) by pyridoxal-5'-phosphate helps to form cystathionine which in turn is converted to cysteine. CBS resides at the intersection of transmethylation, transsulfuration, and remethylation pathways, thus lack of CBS fundamentally blocks Hcy degradation; an essential step in glutathione synthesis. Redox homeostasis, free-radical detoxification and one-carbon metabolism (Methionine-Hcy-Folate cycle) require CBS and its deficiency leads to hyperhomocysteinemia (HHcy) causing retinovascular thromboembolism and eye-lens dislocation along with vascular cognitive impairment and dementia. HHcy results in retinovascular, coronary, cerebral and peripheral vessels' dysfunction and how it causes metabolic dysregulation predisposing patients to serious eye conditions remains unknown. HHcy orchestrates inflammation and redox imbalance via epigenetic remodeling leading to neurovascular pathologies. Although circular RNAs (circRNAs) are dominant players regulating their parental genes' expression dynamics, their importance in ocular biology has not been appreciated. Progress in gene-centered analytics via improved microarray and bioinformatics are enabling dissection of genomic pathways however there is an acute under-representation of circular RNAs in ocular disorders. This study undertook circRNAs' analysis in the eyes of CBS deficient mice identifying a pool of 12532 circRNAs, 74 exhibited differential expression profile, ∼27% were down-regulated while most were up-regulated (∼73%). Findings also revealed several microRNAs that are specific to each circRNA suggesting their roles in HHcy induced ocular disorders. Further analysis of circRNAs helped identify novel parental genes that seem to influence certain eye disease phenotypes.

Benign Reactive Lymphoid Hyperplasia of the Conjunctiva Treated With Cyclosporine.

PURPOSE: To describe a case of reactive lymphoid hyperplasia (RLH) of the conjunctiva responding to cyclosporine immunosuppressant monotherapy. METHODS: A 66-year-old man with a 2-year history of biopsy-proven bilateral RLH presented for dry eye evaluation with chief complaints of burning, stinging, and irritation in both eyes. After slit-lamp examination and positive findings of matrix metalloproteinase 9 in the patient's tear film, he was diagnosed with meibomian gland dysfunction and tear-insufficiency dry eye disease. The patient was subsequently treated with topical cyclosporine (ophthalmic emulsion 0.5 mg/mL two times per day) in both eyes. RESULTS: Examination at the 3-month follow-up visit revealed significant reduction of the RLH lesions bilaterally. CONCLUSIONS: This report represents the first case of benign ocular RLH responsive to topical cyclosporine therapy. We believe that cyclosporine could play a role in treating patients with benign ocular RLH and warrants further investigation to evaluate its full efficacy.

Acute Zonal Cone Photoreceptor Outer Segment Loss.

Importance: The diagnostic path presented narrows down the cause of acute vision loss to the cone photoreceptor outer segment and will refocus the search for the cause of similar currently idiopathic conditions. Objective: To describe the structural and functional associations found in a patient with acute zonal occult photoreceptor loss. Design, Setting, and Participants: A case report of an adolescent boy with acute visual field loss despite a normal fundus examination performed at a university teaching hospital. Main Outcomes and Measures: Results of a complete ophthalmic examination, full-field flash electroretinography (ERG) and multifocal ERG, light-adapted achromatic and 2-color dark-adapted perimetry, and microperimetry. Imaging was performed with spectral-domain optical coherence tomography (SD-OCT), near-infrared (NIR) and short-wavelength (SW) fundus autofluorescence (FAF), and NIR reflectance (REF). Results: The patient was evaluated within a week of the onset of a scotoma in the nasal field of his left eye. Visual acuity was 20/20 OU, and color vision was normal in both eyes. Results of the fundus examination and of SW-FAF and NIR-FAF imaging were normal in both eyes, whereas NIR-REF imaging showed a region of hyporeflectance temporal to the fovea that corresponded with a dense relative scotoma noted on light-adapted static perimetry in the left eye. Loss in the photoreceptor outer segment detected by SD-OCT co-localized with an area of dense cone dysfunction detected on light-adapted perimetry and multifocal ERG but with near-normal rod-mediated vision according to results of 2-color dark-adapted perimetry. Full-field flash ERG findings were normal in both eyes. The outer nuclear layer and inner retinal thicknesses were normal. Conclusions and Relevance: Localized, isolated cone dysfunction may represent the earliest photoreceptor abnormality or a distinct entity within the acute zonal occult outer retinopathy complex. Acute zonal occult outer retinopathy should be considered in patients with acute vision loss and abnormalities on NIR-REF imaging, especially if multimodal imaging supports an intact retinal pigment epithelium and inner retina but an abnormal photoreceptor outer segment.

Pharmacokinetics, urinary excretion and plasma protein binding of ofloxacin in water buffalo calves (Bubalus bubalis).

Pharmacokinetics and urinary excretion of an intravenous dose of 5 mg.kg-1 ofloxacin were investigated in water buffalo calves. Plasma concentrations of ofloxacin were determined by high-performance liquid chromatography. Ofloxacin was rapidly distributed from the central to the peripheral compartment as evidenced by a short distribution half-life (0.09 h ± 0.003 h) and high K12 (4.7 h(-1) ± 0.1 h(-1)), and was detected in plasma for 8 h. The large volume of distribution (2.48 L.kg(-1) ± 0.18 L.kg(-1)) obtained in this study indicated high distribution of ofloxacin in water buffalo calves. The elimination half-life, the area under the plasma drug concentration-time curve and total body clearance were 2.11 h ± 0.13 h, 6.20 µg.mL(-1) ± 0.23 µg.mL(-1).h and 0.81 mL.kg(-1).h(-1) ± 0.03 mL.kg(-1).h(-1), respectively. About 18.7% of administered drug was bound to plasma proteins and approximately 32.5% of the administered dose was recovered in urine within 48 h. The results of the study indicated a favourable pharmacokinetic profile of ofloxacin in water buffalo calves, which suggests that ofloxacin may be effective against urinary pathogens in this species.