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Purpose: To investigate how home optical coherence tomography (OCT) influences the clinical decision-making of retina specialists for the management of neovascular age-related macular degeneration (nAMD). Methods: In this retrospective imaging review, 15 retina specialists each evaluated 10 home OCT data segments from 29 eyes being treated for nAMD. Based on OCT data, indications were identified for when eyes should be treated, which antivascular endothelial growth factor should be used, and the specific retinal fluid and time thresholds for notification. Results: Withholding treatment was recommended in 64 (42.7%) of 150 data segments (95% CI, 34.7-50.6), whereas 100% of eyes received treatment on the last day of each data segment. Treatment was recommended in 86 cases (57.3%), with treatment occurring 7 or more days before the actual treatment was advised in 52 (60.5%) of 86 data segments. This earlier treatment would have prevented the accumulation of intraretinal fluid (IRF), subretinal fluid (SRF), and total retinal fluid for 69.1 nL, 162.2 nL, and 231.2 nL days. Retina specialists chose a different type of treatment agent in 35 (40%) of 86 cases. The following notification values were set: IRF, mean 9.8 ± 14.9 nL (median, 5; IQR, 5); SRF, mean 10.2 ± 16.1 nL (median, 5.5; IQR, 5); total retinal fluid, mean 15.2 ± 24.0 nL (median, 10; IQR, 5). The time-based notification interval was set at a mean of 34.7 ± 21.9 days (median, 30; IQR, 2). Conclusions: Home OCT-based decision-making by retina specialists differed substantially from actual clinical care. Home OCT has the potential to facilitate personalized care in nAMD., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: G: Grant, C: Consultant, H: Honorarium, T: Travel Support, S: Shareholder: A: Advisory or Safety Board Member, L: Leadership. JSH: 4D Molecular Therapuetics (G,C,S), Annexon (G,C), Apellis (G,C), AsclepiX Therapeutics (G,C), Ashvattha (G), Bayer (G), Cognition Therapeutics (G), Curacle (G,C), Genentech/Roche (G,C), Gyroscope Therapeutics (G,C), Iveric Bio (G,C), Janssen R&D (G,C), Kodiak (G), NGM (G,C), Novartis (G,C), OcuTerra (G,C), Perceive Bio (G), Regeneron Pharmaceuticals (G,C), RegenexBio (G,C), Abpro (C), Adverum (C,S), AffaMed Therapeutics (C), Applied Genetics Technologies Corporation (C), Akouos (C), Aviceda (C,S), Bausch + Lomb (C), Biovisics (C), Clearside (C), DTx Pharma (C,S), Exegenesis (C), Glaukos (C), Gyroscope Therapeutics (C), Immunogen (C), jCyte (C,S), Kriya (C), Nanoscope (C), Notal Vision (C), Ocular Therapeutix (C,L), Ocuphire (C,S), OliX (C), ONL Therapeutics (C), Outlook Therapeutics (C), Palatin Technologies (C), Perceive Biotherapeutics (C), Ray Therapeutics (C), RetinAI (C), RevOpsis Therapeutics (C,S), Stealth BioTherapeutics (C), Théa Pharmaceuticals (C), Vanotech (C), Aldeyra Therapeutics (S), Allegro (S), Vinci Pharmaceuticals (S), Vitranu (S); YL: Genentech (H), Horizon Therapeutics (H), Apellis Pharmaceuticals (H), Regeneron Healthcare Solutions (H), Notal Vision (T), Center for Eye Research and Education (T); NMH: Notal Vision (G,A,S);MHA: Notal (M), Alimera Science (C), Abbvie (C); KJB: Notal Vision (M), Regeneron (C,H), Genentech (C,H), Bausch & Lomb (C,H), Biogen (C); MAB: Notal Vision (M,C,H,T); MAC: Notal Vision (M,C); MJE: Notal Vision (G, T); JGF: Notal Vision (M), Roche (C, A, H), Regeneron (C, A, H); PH: Notal Vision (M), Adverum (G,C), Apellis (G,C,A), Eyepoint (G,C,H,A), Genentech (G,C,H,A), Regeneron (G), RegenxBio (G), Samsara (G), Alcon (C,A), DORC (C,A), ASRS (L); NL: Notal Vision (M), Roche (C), Regeneron (C,A), RegenxBio, (C), Ionis (C), Apellis (C,H), Annexon (C), Genentech (H,A), Iveric Bio (H), EyePoint Pharmaceuticals (A), Opthea (A); TM: Notal Vision (M); YSM: Notal Vision (C), Alimera (C), Allergan (C), Genentech (C), DORC (C), Thea (C), Zeiss (C), Iveric Bio (C), Apellis, Regeneron (C); AR: AGTC (G), Apellis Pharmaceuticals (G,C,), DRCR Retina Network (G), Roche/Genentech (G,C), Abbvie/Allergan (C), Alcon (C), Regeneron (C), Iveric Bio (C), Ocular Therapeutix (C); EWS: Notal Vision (M,C), Carl Zeiss (C); JCW: Genetech (C,A), Carl Zeiss (C); ARS: Notal Vision (M,C), RegenxBio (C), Regeneron (C), Apellis (S). The sponsor of the study is a provider of home OCT monitoring services., (© The Author(s) 2024.)

Purpose: To evaluate the incidence and clinical characteristics of intravitreal injection-related endophthalmitis cases with antivascular endothelial growth factor (anti-VEGF) medications manufactured as prefilled syringes or non-prefilled preparations. Methods: This retrospective chart review comprised eyes that received intravitreal anti-VEGF at a single-specialty retina practice from January 1, 2014, to December 31, 2019. Eyes diagnosed with injection-related endophthalmitis were identified. Demographic and clinical data were abstracted from medical records, including the type of anti-VEGF agent, baseline and follow-up corrected visual acuity (VA), and microbiologic findings. Results: The review identified 88 cases of intravitreal anti-VEGF injection-related endophthalmitis and 325 990 total injections. Total injections included 32 045 (9.8%) bevacizumab (BEV), 93 073 (28.6%) ranibizumab (RAN), 122 947 (37.7%) aflibercept (AFL), and 77 925 (23.9%) ranibizumab prefilled syringe (RANPFS). Ten of the endophthalmitis cases were related to BEV, 21 to RAN, 45 to AFL, and 12 to RANPFS. The endophthalmitis rate was lowest for RANPFS (0.0154%) (BEV, 0.0312%; RAN, 0.0226%; AFL, 0.0366%) ( P = .030). Thirty-four (41.5%) of 82 samples were culture positive. RANPFS had a significantly lower rate of culture-proven postinjection endophthalmitis than the other agents ( P = .003). The mean VA for endophthalmitis cases related to RANPFS vs non-prefilled agents was similar at presentation (Snellen 20/2092 vs 20/2327) and at the 3-month follow-up (Snellen 20/201 vs 20/272) (both P > .05). Conclusions: Anti-VEGF medications in prefilled syringes may reduce the risk for medication contamination during injection preparation. RANPFS was associated with a lower rate of injection-related endophthalmitis than non-prefilled anti-VEGF medications., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Roth is a consultant to Alimera Sciences, and has received royalties from Genentech., (© The Author(s) 2023.)

Purpose: The aim of this study was to test the discomfort experienced during intravitreal injections with eyelid retraction between an eyelid speculum, cotton-tipped applicator (CTA), and unimanual eyelid retraction techniques., Methods: In total, 99 patients receiving intravitreal bevacizumab were enrolled into this prospective study. Participants were randomized to one of the three methods, given subconjunctival 2% lidocaine and then injected in the superior temporal quadrant. Immediately after the procedure, each patient was given a visual analog scale (VAS) to rate their discomfort., Results: The mean pain scores for eyelid retraction with unimanual, CTA, and speculum groups were 0.788 (standard deviation [SD] 0.70, 95% confidence interval [CI] 0.448-1.128), 0.945 (SD 1.28, 95% CI 0.600-1.291), and 1.561 (SD 1.28, 95% CI 1.210-1.912), respectively. A one-way analysis of variance (ANOVA) test revealed a significant difference between the groups (P = 0.006). Post hoc analysis also revealed a difference in mean pain scores between the speculum and both the CTA and the unimanual methods., Conclusion: Our study shows that the unimanual and CTA methods for eyelid retraction are significantly less painful for patients compared to the speculum method. Patient comfort is of the utmost importance as intravitreal injections are performed millions of times a year with most patients requiring multiple injections., Competing Interests: None

Purpose: To investigate hyperreflective lesions within the paracentesis and main wound incisions after cataract surgery performed with disposable blades., Setting: Kings County Hospital, Brooklyn, New York, USA., Design: Retrospective study., Methods: This is a retrospective study of 14 patients after cataract surgery with disposable corneal incision blades for the paracentesis and main wound. Anterior segment photographs were reviewed from preoperative and postoperative evaluations. Anterior segment optical coherence tomography (OCT) of the paracentesis and main wounds was included., Results: Fourteen eyes from 14 patients were included in this study. Eleven patients had anterior segment photographs and 2 patients had anterior segment OCT showing hyperreflective lesions within the main wound and paracentesis. One patient had intraoperative photographs showing these hyperreflective lesions appearing immediately after wound construction. No patients had complications related to these findings. Cleaned disposable keratome blades had silicone oil applied to them, and then, main wounds were constructed on pig eyes that showed similar hyperreflective corneal lesions as the 11 patients presented., Conclusions: To the authors' knowledge, this was the first study to show hyperreflective lesions within corneal incisions after anterior segment surgery. The hypothesis was that trace amounts of silicone oil on the disposable blades was the etiology; this did not seem to have any negative consequences for the patients.

Purpose: To evaluate possible associations between primary open-angle glaucoma (POAG), dental health, and the oral microbiome., Methods: Case-control study was conducted at SUNY Downstate. Adult subjects (40 to 87 y) were recruited as POAG cases (n=119) and controls without glaucoma (n=78) based on visual field and optic nerve criteria. Overall 74.6% were African Americans (AA). Information on medical history and oral health was collected and ophthalmologic examinations were performed. Mouthwash specimens (28 AA cases and 17 controls) were analyzed for bacterial DNA amounts. Analyses were limited to AAs as the predominant racial group. Outcome measures included number of natural teeth, self-reported periodontal health parameters, and amounts and prevalence of oral bacterial species. Logistic regression was used to evaluate associated factors and potential interactions., Results: Cases and controls had similar age (mean: 62.2 and 60.9 y, respectively, P>0.48), and frequency of hypertension, diabetes, but cases had a higher proportion of men (P<0.04). On average (±SD), cases had fewer natural teeth than controls [18.0 (±11.1) vs. 20.7 (±9.4)]. Having more natural teeth was inversely associated with POAG, in multivariable analyses, at older ages [eg, odds ratio (95% confidence interval) at age 55: 1.0 (0.95-1.06), P=0.98 vs. at age 85: 0.87 (0.79-0.96), P=0.007]. Amounts of Streptococci were higher in cases than controls (P<0.03) in samples from the subset of subjects analyzed., Conclusions: The number of teeth (an oral health indicator) and alterations in the amounts of oral bacteria may be associated with glaucoma pathology. Further investigation of the association between dental health and glaucoma is warranted.

Behavioral sensitization to psychostimulants is associated with changes in dopamine (DA), glutamate, and GABA within the mesocorticolimbic and nigrostriatal DA systems. Because GABAA receptors are highly expressed within these systems, we examined the role of these receptors containing a δ subunit in cocaine behavioral sensitization. Experiment 1 examined the effects of Gaboxadol (GBX, also known as THIP [4,5,6,7-tetrahydro-isoxazolo[5,4-c]pyridin-3-ol]), a selective δ-GABAA receptor agonist, on the locomotor responses to acute cocaine. GBX at 1.25 mg/kg produced locomotor depression in female rats alone. We then examined the effects of GBX on the expression of cocaine-induced locomotion and stereotypy in female and male rats treated with 5 days of cocaine (15 mg/kg) followed by cocaine challenge 7 days later. We administered systemic (Experiment 2) or intranucleus accumbens (intra-NAC; Experiment 3) injections of GBX (0, 1.25, 2.5, 5, or 10 mg/kg subcutaneously, or 1 μmol/L or 1 mM intra-NAC, respectively) prior to cocaine challenge (10 mg/kg). In our experiments females were robustly sensitized to cocaine at low dose whereas males did not show such sensitization-limiting comparisons between the 2 sexes. Sensitized females showed a biphasic response to low (1.25 mg/kg and 1 μmol/L) and high (10 mg/kg and 1 mM) dose GBX whereas nonsensitized males showed this pattern only following intra-NAC injection. Immunohistochemical analysis of the NAC revealed that females have more δ-containing GABAA receptors than do males and that following chronic cocaine injections this difference persisted (Experiment 4). Together, our results support the notion of the key role of extrasynaptic GABAA δ-subunit containing receptors in cocaine sensitization., ((c) 2016 APA, all rights reserved).)

Purpose: To determine the sex and age-related effects of C1qa ablation on retinal ganglion cell (RGC) and optic nerve (ON) axonal loss in a mouse model of glaucomatous neurodegeneration., Methods: Congenic C1qa mice were generated in the DBA/2NNia background. Female and male knockout (-/-), heterozygous (+/-), and wild type (+/+) mice were aged up to 14 months and IOPs were recorded in a subset of animals. Retinas of mice from all three groups at 5-6, 9-10 and 11-13 months of age were flat-mounted after retrograde labeling with Fluorogold. Imaged retinas were scored (RGC score) semi-quantitatively on a 10 point scale by two independent observers. A subset of retinas and optic nerves were also used for measurement of total number of RGCs. Semi-thin sections of ON were imaged and graded (ON score) for the amount of axonal damage semi-quantitatively, by two masked observers. Analysis of covariance (ANCOVA) was used for statistical comparisons. Microglial cells in flat-mounted retinas of 5-6 month old C1qa -/- and C1qa +/+ mice were used for assessment of microglial activation utilizing morphological criteria., Results: Female C1qa -/- mice had significantly higher IOP (p<0.000001, ANOVA) between 8 and 13 months of age compared to C1qa +/+ animals. No differences in IOPs between animals of the three genotypes were observed in males. At 5-6 months of age, there was no difference in RGC or ON scores between the three genotypes in animals of either sex. At 9-10 months of age, female mice didn't show significant differences in RGC or ON scores between the three genotypes. However, male C1qa -/- and C1qa +/- mice of the same age had better RGC and ON scores (p<0.003 and p<0.05, ANCOVA, for RGC and ON scores, respectively) compared with C1qa +/+ mice. At 11-13 months of age, female C1qa -/- mice had better RGC scores (p<0.006, ANCOVA) compared to C1qa +/+ and C1qa +/- animals. Accordingly, C1qa -/- mice had higher RGC counts (p<0.03, t-test) compared to C1qa +/+ animals. In male mice, there was a tendency for 12 month old C1qa -/- animals to have better RGC scores and higher RGC counts, but this didn't reach statistical significance. ON scores in 11-13 month old animals of either sex were not different between all three genotype. Microglial activation in male 5-6 month old C1qa -/- mice was decreased compared to C1qa +/+ animals; no such effect was seen in females., Conclusions: Absence of C1qa ameliorates RGC and ON loss in the DBA/2NNia strain, but this effect differs between the two sexes. C1q-mediated RGC damage seems to be more potent than IOP-mediated RGC loss. In contrast, C1qa absence provides axonal protection early on, but this protection cannot overcome the effects of significant IOP elevation.

Background: Glaucoma is a progressive optic nerve degenerative disease that often leads to blindness. Local inflammatory responses are implicated in the pathology of glaucoma. Although inflammatory episodes outside the CNS, such as those due to acute systemic infections, have been linked to central neurodegeneration, they do not appear to be relevant to glaucoma. Based on clinical observations, we hypothesized that chronic subclinical peripheral inflammation contributes to neurodegeneration in glaucoma., Methods: Mouthwash specimens from patients with glaucoma and control subjects were analyzed for the amount of bacteria. To determine a possible pathogenic mechanism, low-dose subcutaneous lipopolysaccharide (LPS) was administered in two separate animal models of glaucoma. Glaucomatous neurodegeneration was assessed in the retina and optic nerve two months later. Changes in gene expression of toll-like receptor 4 (TLR4) signaling pathway and complement as well as changes in microglial numbers and morphology were analyzed in the retina and optic nerve. The effect of pharmacologic blockade of TLR4 with naloxone was determined., Findings: Patients with glaucoma had higher bacterial oral counts compared to control subjects (p<0.017). Low-dose LPS administration in glaucoma animal models resulted in enhancement of axonal degeneration and neuronal loss. Microglial activation in the optic nerve and retina as well as upregulation of TLR4 signaling and complement system were observed. Pharmacologic blockade of TLR4 partially ameliorated the enhanced damage., Conclusions: The above findings suggest that the oral microbiome contributes to glaucoma pathophysiology. A plausible mechanism by which increased bacterial loads can lead to neurodegeneration is provided by experiments in animal models of the disease and involves activation of microglia in the retina and optic nerve, mediated through TLR4 signaling and complement upregulation. The finding that commensal bacteria may play a role in the development and/or progression of glaucomatous pathology may also be relevant to other chronic neurodegenerative disorders.

Purpose: To determine whether short-term pressure elevation affects complement gene expression in the retina in vitro and in vivo., Methods: Muller cell (TR-MUL5) cultures and organotypic retinal cultures from adult mice and monkeys were subjected to either 24-h or 72-h of pressure at 0, 15, 30, and 45 mmHg above ambient. C57BL/6 mice were subjected to microbead-induced intraocular pressure (IOP) elevation for 7 days. RNA and protein were extracted and used for analysis of expression levels of complement component genes and complement component 1, q subcomponent (C1q) and complement factor H (CFH) immunoblotting., Results: mRNA levels of complement genes and C1q protein levels in Muller cell cultures remained the same for all pressure levels after exposure for either 24 or 72 h. In primate and murine organotypic cultures, pressure elevation did not produce changes in complement gene expression or C1q and CFH protein levels at either the 24-h or 72-h time points. Pressure-related glial fibrillary acidic protein (GFAP) mRNA expression changes were detected in primate retinal organotypic cultures (analysis of variance [ANOVA]; p<0.05). mRNA expression of several other genes changed as a result of time in culture. Eyes subjected to microbead-induced IOP elevation had no differences in mRNA expression of complement genes and C1q protein levels (ANOVA; p>0.05 for both) with contralateral control and naïve control eyes., Conclusions: Short-term elevation of pressure in vitro as well as short-term (1 week) IOP elevation in vivo does not seem to dramatically alter complement system gene expression in the retina. Prolonged expression to elevated pressure may be necessary to affect the complement system expression.