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Purpose:To evaluate the clinical outcomes of different types of treatment of retinal arterial macroaneurysm with vitreous hemorrhage. Methods:This retrospective cohort study comprised patients with retinal arterial macroaneurysm and vitreous hemorrhage who were examined at a single retina clinic between 2013 and 2021. Results:Treatment arms included observation (n = 33), intravitreal injections (IVIs) of antivascular endothelial growth factor agents (n = 5), and pars plana vitrectomy (PPV; n = 12). Baseline characteristics and final best-corrected visual acuity (BCVA) were similar in a combined analysis of all treatment groups (P> .05). The BCVA improved in all eyes, but the IVI and PPV arms had worse presenting BCVA. The mean number of injections was 3.6 ± 2.8. The incidence of subretinal hemorrhage was 18.2% in the observation arm, 25.0% in the PPV group (8.3% had subretinal tissue plasminogen activator), and 60.0% in the IVI group. The mean time to intervention was 13 ± 15.3 days for PPV and 38 ± 69.9 days for IVI. There was no correlation between the number of injections and the final BCVA (r= 0.13, P= .830). The IVI and PPV arms were more frequently on anticoagulants (P= .011). There was no difference in final BCVA between those using anticoagulants (0.52 ± 0.53) vs not using anticoagulants (0.55 ± 0.65) (P= .870). Conclusions:Most patients, regardless of treatment modality, demonstrated significantly improved BCVA and similar final visual outcomes. Patients with worse presenting BCVA were more likely to undergo PPV or IVI whereas those with better presenting BCVA had excellent outcomes with observation alone. Improved BCVA was not associated with the number of IVIs or anticoagulant use.

Background: Due to the increased resistance against existing antibiotics, research is essentialto discover new and alternative ways to control infections induced by resistant pathogens. Objective: The goal of the current scrutinization was to enrich the dissolution rate and antibacterialproperty of cefixime (CEF) orally. Methods: To achieve the desired results, chitosan nanoparticles (NPs) containing CEF were fabricatedusing the ionic gelation method. Central Composite design has been applied to get the optimalformulation for the delivery of CEF. The effect of three variables, such as the concentration ofchitosan, tripolyphosphate, and tween 80, on the characteristics of NPs was evaluated. Results: The optimized NPs involved a relatively monodispersed size distribution with an averagediameter of 193 nm and a zeta potential of about 11 mV. The scanning tunneling microscope confirmedthe size of NPs. The surface morphology of NPs was observed by scanning electron microscopy.The calorimetric analysis indicated the amorphous state of cefixime in the formulation. Thedissolution rate of NPs in aqueous media was acceptable and the model of release kinetics for CEFfrom NPs followed the Peppas model. The potency of CEF in NPs against various types of bacteriawas hopefully efficient. The ex-vivo release study demonstrated higher penetration of NPs from therat intestine compared to free drug. The cell culture study showed the safety of the optimized formulation. Conclusion: Chitosan NPs could be considered a significant system for the controlled delivery ofCEF due to its antibacterial effectiveness.

Introduction:Trans-scleral biopsy of uveal melanoma (UM) poses an inherent risk of tumor and possibly retinal perforation. We describe a novel technique for trans-scleral biopsy of UM and evaluate its safety and efficacy in an initial cohort of patients. Methods:A retrospective, consecutive observational case series was conducted from October 14, 2019, to April 15, 2020, at Kaiser Permanente, San Francisco, CA among patients with UM of the ciliary body or anterior choroid undergoing trans-scleral fine-needle aspiration biopsy using a novel guarded needle technique. Results:A total of 6 patients were included in the study, with a mean age of 64.3 (range 35–77) years (5 women 83%). Mean (±SD) tumor thickness and maximal basal diameter were 6.4 (±2.66) and 11.9 (±2.13) mm, respectively. Five out of 6 patients achieved a successful biopsy with reliable gene expression profiling (GEP) results. The only failure to obtain specimen occurred in the first attempted patient and, after a minor technique modification, all subsequent biopsies were successful. No intraoperative or short-term postoperative complications were observed in any patient. Conclusion:This novel trans-scleral biopsy technique appears to be safe and effective when obtaining UM tissue for GEP. This method may provide a more controlled biopsy depth thereby minimizing the risk of tumor perforation and its associated complications while still obtaining adequate biopsy yield.

Purpose:To compare the anatomic and visual acuity (VA) outcomes of rhegmatogenous retinal detachment (RRD) repair in eyes with a multifocal intraocular lens (IOLs) and eyes with monofocal IOLs. Methods:This retrospective matched-cohort study comprised pseudophakic eyes that had pars plana vitrectomy (PPV) or PPV with scleral buckling for RRD. Eyes with multifocal IOLs (multifocal group) were matched with eyes with monofocal IOLs (control group) in a 1:2 ratio for age, sex, primary surgeon, timing of surgery from presentation, type of surgery, and macular status. Results:The multifocal group included 67 eyes and the control group, 134 eyes. The mean (±SD) follow-up was 785 ± 595 days and 746 ± 566 days, respectively (P= .57). Overall, the single-surgery anatomic success rate was 76.1% in the multifocal group and 86.6% in the control group (P= .06); 75.0% and 85.9%, respectively, for PPV (P= .06); and 100% for PPV with scleral buckling in both groups (P= 1.00). The mean final logMAR VA was 0.26 ± 0.34 (20/36 Snellen) in the multifocal group and 0.27 ± 0.36 (20/37 Snellen) in the control group (P= .60). Conclusions:In pseudophakic eyes with an RRD, there was a trend toward better single-surgery anatomic success in eyes with a monofocal IOL than in eyes with a multifocal IOL treated with PPV, with similar anatomic outcomes for PPV with scleral buckling. Visual outcomes were similar between the groups and significantly improved compared with baseline.

BACKGROUND AND OBJECTIVE:This study evaluated the residual subfoveal fluid (SFF) immediately after rhegmatogenous retinal detachment (RRD) repair using intraoperative optical coherence tomography (iOCT).PATIENTS AND METHODS:This retrospective cohort study assessed fovea-involving RRD repaired by pars plana vitrectomy (PPV) using different drainage techniques. iOCT images were acquired through the fovea at the start of the case prior to initiating vitrectomy and then again immediately prior to introduction of tamponade.RESULTS:Ten eyes (32.3%) received perfluoro-n-octane (PFO), 12 (38.7%) underwent a posterior drainage retinotomy, and nine (29.0%) had drainage through the retinal break. There was no significant difference in the mean SFF thickness between eyes in either group (Ten eyes (32.3%) received perfluoro-n-octane (PFO), 12 (38.7%) underwent a posterior drainage retinotomy, and nine (29.0%) had drainage through the retinal break. There was no significant difference in the mean SFF thickness between eyes in either group (P= .85). There was no significant association between SFF thickness on iOCT and functional or anatomic outcomes (P> .05).CONCLUSION:There is no difference in the amount of residual SFF as measured on iOCT during RRD repair with pars plana vitrectomy using either direct drainage, drainage retinotomy, or PFO.[[Ophthalmic Surg Lasers Imaging Retina. 2019;50:497–503.]

PurposeTo examine the effect of low-dose, oral isotretinoin in lowering the risk of proliferative vitreoretinopathy (PVR) following rhegmatogenous retinal detachment (RRD) repair.MethodsProspective, open label, dual-cohort study with pathology-matched historical controls. The prospective experimental arms included two cohorts, composed of 51 eyes with recurrent PVR-related RRD and 58 eyes with primary RRD associated with high-risk features for developing PVR. Eyes in the experimental arms received 20 mg of isotretinoin by mouth once daily for 12 weeks starting the day after surgical repair. The primary outcome measure was single surgery anatomical success rate at 3 months following the study surgery.ResultsThe single surgery anatomic success rate was 78.4% versus 70.0% (p=0.358) in eyes with recurrent PVR-related retinal detachment exposed to isotretinoin versus historical controls, respectively. In eyes with RRD at high risk for developing PVR, the single surgery success rate was 84.5% versus 61.1% (p=0.005) for eyes exposed to isotretinoin versus historical controls, respectively. For eyes enrolled in the experimental arms, the most common isotretinoin-related side effects were dry skin/mucus membranes in 106 patients (97.2%), abnormal sleep/dreams in 4 patients (3.7%) and fatigue in 3 patients (2.8%).ConclusionThe management and prevention of PVR is challenging and complex. At the dose and duration given in this study, oral istotretinoin may reduce the risk of PVR-associated recurrent retinal detachment in eyes with primary RRD at high risk of developing PVR.

IMPORTANCE: Loss to follow-up (LTFU) after anti–vascular endothelial growth factor (anti-VEGF) injections increases the risk of vision loss among patients with neovascular age-related macular degeneration (nAMD). OBJECTIVE: To report rates of LTFU among patients with nAMD after anti-VEGF injections and to identify risk factors associated with LTFU in this population. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study of data from 9007 patients who received anti-VEGF injections for treatment of nAMD was performed at an urban, private retina practice with multiple locations from April 1, 2012, to January 12, 2016. MAIN OUTCOMES AND MEASURES: Rates of LTFU after anti-VEGF injections. Loss to follow-up was defined as receipt of 1 or more injections with no subsequent follow-up visit within 12 months. RESULTS: Among the 9007 patients (mean [SD] age, 81.2 [8.8] years; 5917 [65.7%] female; 7905 [87.8%] white), 2003 (22.2%) were LTFU. Odds of LTFU were greater among patients 81 to 85 years of age (odds ratio [OR], 1.58; 95% CI, 1.38-1.82; P < .001), 86 to 90 years of age (OR, 2.29; 95% CI, 2.00-2.62; P < .001), and more than 90 years of age (OR, 3.31; 95% CI, 2.83-3.86; P < .001) compared with patients 80 years of age and younger. Odds of LTFU among African American patients (OR, 1.47; 95% CI, 1.00-2.16; P = .05), Asian patients (OR, 2.63; 95% CI, 1.71-4.03; P < .001), patients of other race (OR, 3.07; 95% CI, 1.38-6.82; P = .006), and patients of unreported race (OR, 2.29; 95% CI, 1.96-2.68; P < .001) were greater than odds of LTFU among white patients. Odds of LTFU were greater among patients with regional adjusted gross income of $50 000 or less (OR, 1.52; 95% CI, 1.30-1.79; P < .001), $51 000 to $75 000 (OR, 1.35; 95% CI, 1.17-1.56; P < .001), and $76 000 to $100 000 (OR, 1.28; 95% CI, 1.08-1.50; P = .004) compared with patients with incomes greater than $100 000. Odds of LTFU for patients living 21 to 30 miles (OR, 1.33; 95% CI, 1.05-1.69; P = .02) and more than 30 miles (OR, 1.55; 95% CI, 1.28-1.88; P < .001) from clinic were greater compared with patients who lived 10 miles or less from the clinic. Odds of LTFU were greater among patients who received unilateral injections (OR, 1.44; 95% CI, 1.28-1.61; P < .001) than among patients who received bilateral injections. CONCLUSIONS AND RELEVANCE: We found a high rate of LTFU after anti-VEGF injections among patients with nAMD and identified multiple risk factors associated with LTFU among this population. Although our results may not be generalizable, data on LTFU in a clinical practice setting are needed to understand the scope of the problem so that interventions may be designed to improve outcomes.

Purpose: To investigate how the optical density ratio (ODR) of subretinal fluid (SRF) obtained by optical coherence tomography (OCT) in eyes with chronic central serous retinopathy (CSR), defined as symptoms >3 months, treated with eplerenone correlates with treatment response and visual outcomes.Methods: This retrospective, single-center observational study included patients with chronic CSR treated with eplerenone who had at least 6 weeks of follow-up. Eyes with poor-quality OCT scans, shallow SRF precluding sampling of optical density (OD), and macular pathology other than CSR were excluded. Optical density of the vitreous and SRF was measured using ImageJ and used to calculate ODR (ODR = ODSRF/ODVIT). Peak SRF height, foveal SRF height, central macular thickness (CMT), and Snellen visual acuity (VA) were measured. The Mann-Whitney Utest was used to compare continuous variables. Pearson correlation coefficient was used to determine the statistical significance of applied linear regressions.Results: Twenty-three eyes of 23 patients met the inclusion criteria. Six (26%) eyes had complete resolution of foveal SRF (resolvers) with eplerenone treatment, and the remainder of patients had worsening or incomplete resolution (nonresolvers). Resolvers had significantly lower baseline logarithm of the minimum angle of resolution (logMAR) VA (P< .01) than nonresolvers. There was a positive linear correlation between ODR and logMAR VA at baseline (R2= 0.208; P= .03) and follow-up (R2= 0.206; P= .03). A significant correlation between ODR and percentage change in CMT was found (R2= 0.263; P= .01). Linear correlations were not found between ODR and age, peak SRF height, and foveal SRF height (all P> .125).Conclusion: Lower baseline ODR was associated with improved percentage change in CMT and VA in patients treated with eplerenone for chronic CSR. Optical density ratio may represent a novel prognostic biomarker that may help determine which eyes with chronic CSR may respond better to eplerenone.

To evaluate the usefulness of the video indirect ophthalmoscope (VIO) to improve resident ophthalmologist skill with indirect ophthalmoscopy (IO) and scleral depression (SD).

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With the ability to noninvasively visualize vascular flow, optical coherence tomography angiography could serve as a new diagnostic tool for current ophthalmic research and clinical practice. The authors describe and compare optical coherence tomography angiography features in three patients with branch retinal vein occlusion.

The authors report a case of a bilateral occipital pole stroke causing central vision loss with homonymous changes detected with microperimetry. In cases of unexplained central vision loss, microperimetry testing may be helpful in the diagnosis of cerebrovascular disease because of its increased sensitivity for detection of subtle changes suggestive of a homonymous hemianopia.

AimsTo quantify the change in drusen volume over time and identify its prognostic value for individual risk assessment.MethodsA prospective observational study over a minimum of 3 years and maximum of 5 years and follow-up examination every 3 months was conducted at the ophthalmology department of the Medical University of Vienna. 109 patients presenting early and intermediate age-related macular degeneration (AMD) were included, of which 30 patients concluded a regular follow-up for at least 3 years. 50 eyes of 30 patients were imaged every 3 months using spectral-domain and polarisation-sensitive optical coherence tomography (OCT). Drusen volume was measured using an automated algorithm. Data of a 6-month follow-up were segmented manually by expert graders.ResultsGradings from 24 000 individual B-scans showed solid correlation between manual and automated segmentation with an initial mean drusen volume of 0.17 mm3. The increase in drusen volume was shown to be comparable among all eyes, and a model for long-term drusen volume development could be fitted as a cubic polynomial function and an R2=0.955. Spontaneous drusen regression was observed in 22 of 50 eyes. In this group, four eyes developed choroidal neovascularisation and three geographic atrophy.ConclusionsDrusen volume increase over time can be described by a cubic function. Spontaneous regression appears to precede conversion to advanced AMD. OCT might be a promising tool for predicting the individual risk of progression of AMD.

To evaluate the appropriateness and readability of the medical knowledge provided by ChatGPT-4, an artificial intelligence-powered conversational search engine, regarding common vitreoretinal surgeries for retinal detachments (RDs), macular holes (MHs), and epiretinal membranes (ERMs).

IMPORTANCE: There is a subset of eyes with neovascular age-related macular degeneration (AMD) that have persistent exudation despite fixed-interval intravitreous anti–vascular endothelial growth factor (VEGF) injections. OBJECTIVE: To evaluate the effect of topical dorzolamide hydrochloride–timolol maleate on anatomic and functional outcomes in eyes with neovascular AMD and incomplete response to anti-VEGF therapy. DESIGN, SETTING, AND PARTICIPANTS: An exploratory, prospective single-arm interventional study at a tertiary referral academic private practice. Patients with neovascular AMD and persistent macular edema despite fixed-interval intravitreous anti-VEGF therapy were enrolled. Baseline spectral-domain optical coherence tomography and clinical data, including visual acuity and intraocular pressure, were obtained at enrollment and from one visit before enrollment. The study was performed at the Retina Service of Wills Eye Hospital and the offices of Mid Atlantic Retina from February 1, 2015, through September 30, 2015. Patients were followed up for at least 2 visits after enrollment. Central subfield thickness, maximum subretinal fluid height, and maximum pigment epithelial detachment height from spectral-domain optical coherence tomography were recorded at each visit. INTERVENTIONS: Enrolled eyes received a regimen of topical dorzolamide-timolol twice daily and continued to receive the same intravitreous anti-VEGF therapy at the same interval as received before enrollment for the duration of the study. MAIN OUTCOMES AND MEASURES: Change in central subfield thickness was the primary outcome measure. Changes in maximum subretinal fluid height, maximum pigment epithelial detachment height, and visual acuity were the secondary outcome measures. RESULTS: Ten patients (10 eyes) completed the study. The mean age of the patients was 78.2 years (age range, 65-91 years), and 6 were male. Eight eyes received intravitreous aflibercept, and 2 eyes received intravitreous ranibizumab. All study eyes had been receiving long-term anti-VEGF therapy with the same medication before study enrollment for a mean of 21.9 injections. The mean central subfield thickness decreased from 419.7 μm at enrollment to 334.1 μm at the final visit (P = .01). The mean maximum subretinal fluid height decreased from 126.6 μm at enrollment to 49.5 μm at the final visit (P = .02). The mean maximum pigment epithelial detachment height decreased from 277.4 μm at enrollment to 239.9 μm at the final visit (P = .12). The mean logMAR visual acuity were 0.54 at enrollment and 0.48 at the final visit (P = .60). CONCLUSIONS AND RELEVANCE: These data suggest that topical dorzolamide-timolol may reduce central subfield thickness and subretinal fluid in eyes with persistent exudation despite consistent, fixed-interval intravitreous anti-VEGF treatment for neovascular AMD.

The taxanes are chemotherapeutic agents that may, in rare cases, cause cystoid macular edema without leakage on fluorescein angiography. Two patients with evidence of taxane-related macular edema presented and were evaluated using novel en face optical coherence tomography (OCT) and OCT angiography (OCTA) imaging modalities. Although OCTA revealed no flow abnormalities in either patient, en face OCT revealed a striking bilateral symmetric cystic tessellation pattern.[[Ophthalmic Surg Lasers Imaging Retina. 2016;47:176–179.]

The authors describe a case of para-central acute middle maculopathy (PAMM) in a 75-year-old man who had recently undergone cardiac catheterization. Imaging with simultaneous en face optical coherence tomography (OCT) and OCT angiography (OCTA) revealed signal abnormalities localized to the deep capillary plexus. This case highlights the ability of OCTA to image and localize retinal disease by vascular distribution, previously difficult with conventional fluorescein angiography, and lends evidence to the belief that PAMM is caused by vascular injury to the intermediate and deep capillary plexus.[[Ophthalmic Surg Lasers Imaging Retina. 2015;46:972–975.]

A patient presented with sudden ipsilateral vision loss after nasal fat pad cosmetic filler injection. Examination and ancillary testing revealed evidence of multiple branch retinal artery occlusions with associated paracentral acute middle maculopathy.

Both acute rejection (AR) and major infection events (MIE) can reduce long-term allograft survival. We assessed the simultaneous efficacy of serum and urine biomarker indoleamine 2,3-dioxygenase (IDO) enzyme activity and peripheral blood CD4-ATP levels for AR and MIE association, respectively.

To describe a rare case of multifocal juvenile xanthogranuloma (JXG) in a neonate presenting with a large hand mass, bilateral vitreous hemorrhage, and posterior segment involvement.

A 59-year-old patient with bilateral worsening diabetic macular edema received intravitreal injection of aflibercept (Eylea; Regeneron, Tarrytown, NY) to the left eye only. On 1-month follow-up, there was noted bilateral improvement of visual acuity and diabetic macular edema on spectral-domain optical coherence tomography imaging, reflecting bilateral effect of unilateral treatment with aflibercept.[[Ophthalmic Surg Lasers Imaging Retina.2016;47:474–476.]

As folic acid receptors are overexpressed in various cancers including the colon, therefore, nanoparticles of folic acid-polyethylene glycol -poly lactic-co-glycolic acid were fabricated and loaded with irinotecan by emulsification/solvent evaporation technique to target the folic acid receptors in colorectal tumors. The chemical structure of synthesized polymer was examined by 1H NMR, and Box-Behnken design was utilized to determine the combined impact of independent variables for choosing the appropriate formulation. Dynamic light scattering, scanning electron microscope and differential scanning calorimetry (DSC) were utilized to scrutinize irinotecan in nanoparticles. The Box-Behnken design indicated a reasonable correlation between the predicted and experimented values which proves the efficiency of the selected statistical model. The optimized nanoparticles had an acceptable size and morphology. DSC analysis exhibited that irinotecan in nanoparticles is in an amorphous state. The optimized formulation exhibited a prolonged release profile. In addition, the higher drug release from nanoparticles in acidic pH indicates that they can be used to target the extracellular pH of the tumor. The activity of targeted nanoparticles against tumors was higher than the irinotecan and simple nanoparticles. Evaluation of folic acid decorated nanoparticles containing irinotecan confirmed their suitability for targeted delivery of irinotecan in folate positive cancers.

Abstract.: A non-parametric method for the analysis of blocked factorial experiments, based on ranking within blocks, is proposed and shown to be equivalent to partitioning Friedman's test statistic into a set of contrasts reflecting polynomial components of the main effects and interaction. A slightly modified version of the procedure is suggested to partially overcome the problem of loss of power to detect one component when the model includes other components. This alternative procedure is shown to be equivalent to applying a standard normal theory analysis of variance to the ranks. The null distributions and power comparisons are investigated using simulation methods, and it is shown that the non-parametric methods are almost as powerful as the analysis of variance.

Abstract: Chylous reflux is a manifestation of primary or secondary lymphatic obstruction. Primary lymphatic obstruction is defined as lymphangiectasia and incompetency of lymphatic valves without an underlying cause. Lymphangiectasia resulting from trauma, neoplasm, irradiation, or inflammation characterizes secondary lymphatic obstruction. Leakage of chyle into the uterus, vagina, bladder, or rectum can occur with either primary or secondary lymphatic obstruction. We report a patient with chylous vaginal discharge, a rare presentation of primary chylous reflux syndrome. CT-lymphangiography and magnetic resonance imaging clearly depicted this disorder. To our knowledge, only 20 cases of chylous vaginal discharge have been reported previously; chylous vaginal drainage occurred in the absence of chylous uterine reflux in only three. Although this is a rare anomaly, chylous reflux should be considered in a child with chronic vaginal discharge and lower extremity swelling.

Lebowitz: Sensei Biotherapeutics: Employment. Malhotra:Sensei Biotherapeutics: Employment. Fuller:Sensei Biotherapeutics: Employment. Shahlaee:Sensei Biotherapeutics: Equity Ownership; Sensei Biotherapeutics: Consultancy. Ghanbari:Sensei Biotherapeutics: Employment; Sensei Biotherapeutics: Equity Ownership. Emadi:NewLink Genetics: Research Funding.

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