Reduced Incidence of Intravitreal Injection-Related Endophthalmitis With Prefilled Syringes.

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.

EFFECT OF PHYSICIAN FACE MASK USE ON POSTINJECTION ENDOPHTHALMITIS.

PURPOSE: To examine the impact of physician face mask use on the rates and outcomes of postinjection endophthalmitis. METHODS: A multicenter retrospective, comparative cohort study comparing endophthalmitis rate and visual acuity of eyes that developed endophthalmitis after antivascular endothelial growth factor injections at Mayo Clinic Rochester (MCR) and at Mayo Clinic Health System sites depending on physician masking. RESULTS: A total of 164,824 injections were performed at MCR and Mayo Clinic Health System sites. Of these, 66,098 injections were in the no mask group and 98,726 injections were in the mask group. Overall, there were no differences in the rates of infectious endophthalmitis in the no mask versus mask cohorts (overall: no mask: 20 cases [0.0303%] vs. mask: 41 cases (0.0415%); P = 0.24; infectious: no mask: 12 cases [0.018%] versus mask: 13 cases [0.0132%]; P = 0.42). At MCR alone, there was a significant reduction in infectious endophthalmitis between the no mask versus mask groups (no mask: 9 cases [0.0297%] versus mask: 2 cases [0.003%]; P < 0.001). Only 2 cases of infectious endophthalmitis occurred at MCR after the face mask policy was implemented (1 in 30,000 injections). At presentation and at 6 months, the average visual acuity was similar for patients who developed endophthalmitis between the no mask versus mask groups. CONCLUSION: Physician face mask use did not affect the rate or outcome of postinjection endophthalmitis. However, there was a significant reduction at MCR after masking along with other quality improvement measures, including performance of injections in a dedicated procedure room and preparation of patients by nurses, that led to a low rate of endophthalmitis.

Angiographic dark choroid in systemic non-hereditary amyloidosis.

PURPOSE: To describe a novel finding of angiographic dark choroid in a patient with systemic non-hereditary amyloidosis. OBSERVATION: A 43-year old female with systemic light-chain amyloidosis associated with advanced kidney disease presented with metamorphopsia and blurry vision in both eyes of 1 year duration. Examination revealed subretinal yellowish deposits in the central macula and mid-periphery with patchy RPE mottling bilaterally. OCT demonstrated thickened choroid with a widened hyporeflective sub-Bruch's choriocapillaris band. FAF showed hypoautofluorescence of the central maculae with hyperautofluorescence flecks perifoveally. Fluorescein angiography demonstrated normal vascular filling without leakage and peripheral microaneurysms. The FA also revealed a strikingly diminished diffuse lack of choroidal fluorescence throughout all angiographic phases in both eyes which has not been previously described in this condition. CONCLUSIONSAND IMPORTANCE: This case demonstrates that patients with systemic amyloidosis may exhibit attenuation of choroidal signal ("dark choroid") on fluorescein angiography, possibly due to accumulation of amyloid material in the sub-RPE space.

Ultra-low-dose (boom-boom) radiotherapy for management of recurrent ocular post-transplant lymphoproliferative disorder.

PURPOSE: To report a case of recurrent iris post-transplant lymphoproliferative disorder (PTLD) treated with ultra-low-dose (boom-boom) radiotherapy (RT). OBSERVATIONS: A 12-year-old Caucasian male with a history of bilateral, recurrent iris PTLD of the extranodal marginal zone lymphoma (MALT) type presented with persistent bilateral anterior chamber cellular infiltration, which was incompletely controlled on topical corticosteroids, and with elevated intraocular pressure (IOP) in the right eye secondary to steroid response. The patient was diagnosed with PTLD recurrence and was successfully treated with ultra-low-dose RT to both eyes in 2 fractions of 2 Gy. At 15 month follow-up the patient maintained complete disease control with normal IOP off all topical ophthalmic medications. CONCLUSIONS AND IMPORTANCE: Ultra-low-dose RT for ocular PTLD of the MALT subtype represents a novel therapeutic approach that may provide a durable treatment response and could be considered as either primary or adjuvant therapy for this rare condition.

Eyelid retraction discomfort with cotton-tipped applicator, unimanual and speculum intravitreal injection techniques: Eyelid retraction technique randomized comparison trial (Eyelid RETRACT).

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.

Post-cataract surgery hyperreflective lesions within corneal incisions suspected to be silicone oil from disposable blades.

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.

Visual Loss Induced by Adalimumab Used for Plaque Psoriasis.

A 61-year-old Caucasian male with severe plaque psoriasis without joint involvement was initiated on adalimumab therapy. Shortly thereafter he presented to the emergency room with acute loss of vision in the right eye. A comprehensive systemic workup was instituted which included magnetic resonance imaging (MRI) with and without gadolinium of the brain and orbits. MRI revealed findings that were consistent with CNS demyelination and retrobulbar optic neuritis. Immediate cessation of adalimumab was instituted without any other systemic therapy. Complete return of vision occurred within 6 weeks. No additional psoriatic or neurologic treatment was instituted, and the patient has remained stable now for 14 months.

A Pilot Study to Evaluate the Oral Microbiome and Dental Health in Primary Open-Angle Glaucoma.

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.

Effects of gaboxadol on the expression of cocaine sensitization in rats.

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.

Differential Effects of C1qa Ablation on Glaucomatous Damage in Two Sexes in DBA/2NNia Mice.

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.

Oral microbiome link to neurodegeneration in glaucoma.

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.

Complement expression in the retina is not influenced by short-term pressure elevation.

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.