PURPOSE\nTo measure macular choroidal thickness in normal eyes at different points using enhanced depth imaging (EDI) optical coherence tomography (OCT) and to evaluate the association of choroidal thickness and age.\n\n\nDESIGN\nRetrospective, observational case series.\n\n\nMETHODS\nEDI OCT images were obtained in patients without significant retinal or choroidal pathologic features. The images were obtained by positioning a spectral-domain OCT device close enough to the eye to acquire an inverted image. Seven sections were obtained within a 5 x 30-degree area centered at the fovea, with 100 scans averaged for each section. The choroid was measured from the outer border of the retinal pigment epithelium to the inner scleral border at 500-microm intervals of a horizontal section from 3 mm temporal to the fovea to 3 mm nasal to the fovea. Statistical analysis was performed to evaluate variations of choroidal thickness at each location and to correlate choroidal thickness and patient age.\n\n\nRESULTS\nThe mean age of the 30 patients (54 eyes) was 50.4 years (range, 19 to 85 years), and 14 patients (46.7%) were female. The choroid was thickest underneath the fovea (mean, 287 microm; standard deviation, +/- 76 microm). Choroidal thickness decreased rapidly in the nasal direction and averaged 145 microm (+/- 57 microm) at 3 mm nasal to the fovea. Increasing age was correlated significantly with decreasing choroidal thickness at all points measured. Regression analysis suggested that the subfoveal choroidal thickness decreased by 15.6 microm for each decade of life.\n\n\nCONCLUSIONS\nChoroidal thickness seems to vary topographically within the posterior pole. The thickness of the choroid showed a negative correlation with age. The decrease in the thickness of the choroid may play a role in the pathophysiologic features of various age-related ocular conditions.

Enhanced Depth Imaging Optical Coherence Tomography of the Choroid in Normal Eyes

Importance There is no specific antiviral therapy recommended for coronavirus disease 2019 (COVID-19). In vitro studies indicate that the antiviral effect of chloroquine diphosphate (CQ) requires a high concentration of the drug. Objective To evaluate the safety and efficacy of 2 CQ dosages in patients with severe COVID-19. Design, Setting, and Participants This parallel, double-masked, randomized, phase IIb clinical trial with 81 adult patients who were hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was conducted from March 23 to April 5, 2020, at a tertiary care facility in Manaus, Brazilian Amazon. Interventions Patients were allocated to receive high-dosage CQ (ie, 600 mg CQ twice daily for 10 days) or low-dosage CQ (ie, 450 mg twice daily on day 1 and once daily for 4 days). Main Outcomes and Measures Primary outcome was reduction in lethality by at least 50% in the high-dosage group compared with the low-dosage group. Data presented here refer primarily to safety and lethality outcomes during treatment on day 13. Secondary end points included participant clinical status, laboratory examinations, and electrocardiogram results. Outcomes will be presented to day 28. Viral respiratory secretion RNA detection was performed on days 0 and 4. Results Out of a predefined sample size of 440 patients, 81 were enrolled (41 [50.6%] to high-dosage group and 40 [49.4%] to low-dosage group). Enrolled patients had a mean (SD) age of 51.1 (13.9) years, and most (60 [75.3%]) were men. Older age (mean [SD] age, 54.7 [13.7] years vs 47.4 [13.3] years) and more heart disease (5 of 28 [17.9%] vs 0) were seen in the high-dose group. Viral RNA was detected in 31 of 40 (77.5%) and 31 of 41 (75.6%) patients in the low-dosage and high-dosage groups, respectively. Lethality until day 13 was 39.0% in the high-dosage group (16 of 41) and 15.0% in the low-dosage group (6 of 40). The high-dosage group presented more instance of QTc interval greater than 500 milliseconds (7 of 37 [18.9%]) compared with the low-dosage group (4 of 36 [11.1%]). Respiratory secretion at day 4 was negative in only 6 of 27 patients (22.2%). Conclusions and Relevance The preliminary findings of this study suggest that the higher CQ dosage should not be recommended for critically ill patients with COVID-19 because of its potential safety hazards, especially when taken concurrently with azithromycin and oseltamivir. These findings cannot be extrapolated to patients with nonsevere COVID-19. Trial Registration ClinicalTrials.gov Identifier:NCT04323527

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Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Randomized Clinical Trial.

https://serval.unil.ch/resource/serval:BIB_3A01220E0FF1.P001/REF.pdf

Central serous chorioretinopathy: Recent findings and new physiopathology hypothesis.

Objective  To develop a practical evidence based list of clinical risk factors that can be assessed by a clinician at ≤16 weeks’ gestation to estimate a woman’s risk of pre-eclampsia. Design  Systematic review and meta-analysis of cohort studies. Data sources  PubMed and Embase databases, 2000-15. Eligibility criteria for selecting studies  Cohort studies with ≥1000 participants that evaluated the risk of pre-eclampsia in relation to a common and generally accepted clinical risk factor assessed at ≤16 weeks’ gestation. Data extraction  Two independent reviewers extracted data from included studies. A pooled event rate and pooled relative risk for pre-eclampsia were calculated for each of 14 risk factors. Results  There were 25 356 688 pregnancies among 92 studies. The pooled relative risk for each risk factor significantly exceeded 1.0, except for prior intrauterine growth restriction. Women with antiphospholipid antibody syndrome had the highest pooled rate of pre-eclampsia (17.3%, 95% confidence interval 6.8% to 31.4%). Those with prior pre-eclampsia had the greatest pooled relative risk (8.4, 7.1 to 9.9). Chronic hypertension ranked second, both in terms of its pooled rate (16.0%, 12.6% to 19.7%) and pooled relative risk (5.1, 4.0 to 6.5) of pre-eclampsia. Pregestational diabetes (pooled rate 11.0%, 8.4% to 13.8%; pooled relative risk 3.7, 3.1 to 4.3), prepregnancy body mass index (BMI) >30 (7.1%, 6.1% to 8.2%; 2.8, 2.6 to 3.1), and use of assisted reproductive technology (6.2%, 4.7% to 7.9%; 1.8, 1.6 to 2.1) were other prominent risk factors. Conclusions  There are several practical clinical risk factors that, either alone or in combination, might identify women in early pregnancy who are at “high risk” of pre-eclampsia. These data can inform the generation of a clinical prediction model for pre-eclampsia and the use of aspirin prophylaxis in pregnancy.

https://www.bmj.com/content/bmj/353/bmj.i1753.full.pdf

Clinical risk factors for pre-eclampsia determined in early pregnancy: systematic review and meta-analysis of large cohort studies

https://jcp.bmj.com/content/jclinpath/33/9/907.1.full.pdf

Principles and Practice of Infectious Diseases

In this report, we explore retinoblastoma diagnostic accuracy and review chemotherapy alternatives for retinoblastoma using intravenous, intra-arterial, periocular, and intravitreal routes. A review of 2775 patients referred for management of retinoblastoma, disclosed 78% with confirmed retinoblastoma and 22% with simulating lesions, termed pseudoretinoblastomas. Children ≤2 years old showed leading pseudoretinoblastomas of persistent fetal vasculature, Coats disease, and vitreous haemorrhage, whereas those >5 years showed simulators of Coats, toxocariasis, and familial exudative vitreoretinopathy. The diagnosis of retinoblastoma should be established before planning therapeutic strategy. Chemotherapy strategy depends on tumour laterality and stage of disease. If bilateral retinoblastoma, intravenous chemotherapy (IVC) is important as first-line therapy for control of intraocular disease, prevention of metastasis, and reduction in prevalence of pinealoblastoma and long-term second malignant neoplasms. Bilateral groups D and E retinoblastoma receive additional subtenon's carboplatin boost for improved local control. If unilateral disease is present, then intra-arterial chemotherapy (IAC) is often considered. IAC can be salvage therapy following chemoreduction failure. Unilateral retinoblastoma of groups D and E are managed with enucleation or globe-conserving IVC and/or IAC. Intravitreal chemotherapy is cautiously reserved for recurrent vitreous seeds following other therapies. In conclusion, the strategy for retinoblastoma management with chemotherapy depends on tumour laterality and stage of disease. Bilateral retinoblastoma is most often managed with IVC and unilateral retinoblastoma with IAC, but if advanced stage, combination IVC plus IAC or enucleation.

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Retinoblastoma frontiers with intravenous, intra-arterial, periocular, and intravitreal chemotherapy

To measure the choroidal thickness and ocular perfusion pressure in eyes with polypoidal choroidal vasculopathy (PCV), wet-age-related macular degeneration (AMD), and age-matched normal subjects, and look for a possible association between the two. This was a prospective study including 22 eyes with PCV, 33 eyes with wet-AMD, and 35 age-matched normal eyes. Choroidal thickness was measured using enhanced depth imaging (EDI) with spectral-domain optical coherence tomography (SD OCT). Mean ocular perfusion pressure (MOPP) was calculated using the mathematical formula 2/3[DBP+1/3{SBP × DBP}]−IOP (DBP—diastolic blood pressure, SBP—systolic blood pressure, IOP—intraocular pressure). Analyses were carried out using SPSS 14 software and comparisons of mean made using‘t’ tests. Eyes with PCV showed increased (285.9 μm; subfoveal) choroidal thickness, whereas eyes with wet-AMD (119.4 μm; subfoveal) showed reduced choroidal thickness in comparison with normal eyes (186.77 μm; subfoveal). MOPP in the PCV group was 57.85 mm Hg (P value 0.00), in the wet-AMD group was 52.1 mm Hg (P-value 0.12), and in the normal group was 49.79 mm Hg. It is postulated that higher MOPP in eyes with PCV could have an etiologic implication in disease manifestation and progression. Larger studies with longer follow-up may help validate these findings.

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Ocular perfusion pressure and choroidal thickness in eyes with polypoidal choroidal vasculopathy, wet-age-related macular degeneration, and normals.

PURPOSE. Lysyl oxidase (LOX) cross-links the side chain of collagen and elastin and thereby contributes to extracellular matrix (ECM) integrity. ECM remodeling is seen in various ocular diseases. Until now, there have been no reports on the LOX enzyme’s activity in ocular tissues. The purpose of this study was to estimate LOX activity and expression in human donor ocular tissues and to measure the specific activity of LOX in the vitreous of proliferative diabetic retinopathy (PDR) and rhegmatogenous retinal detachment (RRD). METHOD. Human donor eyeballs obtained from an eye bank were used to study tissue distribution of LOX. Human vitreous specimens were obtained during vitreoretinal surgery from PDR (n 16) and RRD (n 10). LOX activity was estimated by N-acetyl-3,7-dihydroxyphenoxazine assay, immunohistochemistry, and real-time polymerase chain reaction (RT-PCR). Matrix metalloprotease (MMP)-2 and -9 were quantified in the vitreous by sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS. The specific activity of LOX in ocular tissues was on the order of vitreous, iris ciliary body, lens, choroid RPE, and retina, which were comparable by mRNA expression and immunolocalization. The vitreous level of LOX activity decreased significantly in PDR and RRD, with an increase in total MMP-2 and -9 levels compared with normal donor vitreous. CONCLUSIONS. LOX activity showed a statistically significant decrease in the vitreous of PDR and RRD relative to control specimens. This effect can contribute to the inadequate collagen cross-linking that causes the ECM changes that occur in these diseases. (Invest Ophthalmol Vis Sci. 2008;49: 4746 – 4752) DOI:10.1167/iovs.07-1550

Lysyl oxidase activity in the ocular tissues and the role of LOX in proliferative diabetic retinopathy and rhegmatogenous retinal detachment.

Primary transpupillary thermotherapy for choroidal melanoma in 391 cases: importance of risk factors in tumor control.

To describe the clinical features and outcomes among eyes with choroidal neovascularization (CNV) in children and adolescents. A total of 36 eyes of 27 patients <18 years of age diagnosed with CNV between January 1978 and December 2008 were retrospectively reviewed. CNV was clinically diagnosed in all patients and its presence was confirmed by fundus fluorescein angiography (FFA). A total of 19 eyes underwent treatment. Anatomical outcome was evaluated as regressed/persistent/recurrent CNV. Snellen’s values for best corrected visual acuity (BCVA) were converted to logMAR for statistical calculations. Of the 27 patients, 17 (63%) were male. Nine (33.3%) of the 27 patients had bilateral CNV. At presentation, CNV was active in 22 (61.1%) eyes and regressed in 14 (28.9%) eyes. All active CNV cases were ‘classic’ type, with the majority (80.5%) being subfoveal. The mean greatest linear dimension (GLD) was 3.16±1.94 mm (range, 0.9–10.15). The most common cause (41.7%) was post-inflammatory. The mean duration to regression in treated eyes was 103.53 days (15 eyes). Recurrence was noted in three (8.3%) eyes. The mean duration to first recurrence was 260 days (range, 90–390), and the mean follow-up duration was 779.53±988.00 days. CNV remains a cause of significant visual decline in children and adolescents. Male predominance, post-inflammatory etiology, bilateral affection, and subfoveal location are noteworthy, with a high regression rate in response to treatment. Re-treatment is required in a limited number of cases.

/pdf/choroidal-neovascularization-in-36-eyes-of-children-and-4zo1dvof34.pdf

Pukhraj Rishi

Papers

Retinoblastoma frontiers with intravenous, intra-arterial, periocular, and intravitreal chemotherapy

Ocular perfusion pressure and choroidal thickness in eyes with polypoidal choroidal vasculopathy, wet-age-related macular degeneration, and normals.

Lysyl oxidase activity in the ocular tissues and the role of LOX in proliferative diabetic retinopathy and rhegmatogenous retinal detachment.

Primary transpupillary thermotherapy for choroidal melanoma in 391 cases: importance of risk factors in tumor control.

Choroidal neovascularization in 36 eyes of children and adolescents