Povidone-iodine in vitro antiseptic efficacy as a function of exposure duration, concentration, preparation, and length of storage.

PURPOSE: Although 5% povidone-iodine (PVP-I) is frequently used as an ocular antiseptic agent, there is a lack of consensus regarding the effects of PVP-I concentration, storage after opening, and compounded preparation on PVP-I antisepsis. We performed a series of in-vitro experiments to determine the impact of these factors on PVP-I's inhibition of common causes of post-procedural eye infection. METHODS: Inhibition of microorganism growth was measured in-vitro as a function of active PVP-I exposure time. In control experiments, PVP-I was inactivated before microorganism exposure. Tested PVP-I solutions varied in concentration (0.6%, 5%, or 10%), length of storage after opening (0, 7, or 30 days), and preparation (commercial vs.compounded from stock PI solution). Tested pathogens included S. epidermidis, S. viridans, P. aeruginosa, methicillin-resistant S. aureus, methicillin-sensitive S. aureus, and C. albicans. RESULTS: PVP-I solutions inhibited all bacterial growth by 3 min and fungal growth by 15 s. Compared to 5% PVP-I, the 0.6% PVP-I was less effective in inhibiting S. viridans growth (200 ± 0 colonies vs. 7 ± 8 at 30 s, P = 0.0004; 183 ± 21 vs. 0 ± 0 at 1 min, P = 0.018), but more effective in inhibiting P. aeruginosa (30 ± 20 vs. 200 ± 0 at 15 s, P = 0.019). Compared to commercial and newly-opened PVP-I solutions, compounded preparations and solutions stored for 7 or 30 days after bottle opening either preserved or improved antiseptic efficacy against tested microorganisms. CONCLUSIONS: Concentration of PVP-I solution affects antiseptic efficacy within 1 min of exposure, but all solutions performed equivalently at 3 min. In contrast to results of prior studies investigating dilute PVP-I, the 0.6% PVP-I did not demonstrate a uniformly equivalent or superior anti-septic effect. Compounded preparation and storage length after bottle opening did not decrease PVP-I antiseptic activity.

Risk factors for enucleation or evisceration in endophthalmitis.

PURPOSE: To identify clinical risk factors for enucleation or evisceration in patients with endophthalmitis at an academic institution. METHODS: A retrospective review of patients diagnosed with endophthalmitis at Wilmer Eye Institute from 2010 to 2019 was conducted. Clinical characteristics, including demographics, cause for endophthalmitis, microbial culture results, salvaging procedures and surgical intervention were recorded. In patients who underwent enucleation or evisceration, type of surgery and placement of a primary implant were recorded. Chi-squared, Student's t-tests and multivariate analysis were used to identify clinical factors that predicted enucleation or evisceration. RESULTS: Two hundred and fifty three patients treated for endophthalmitis over the study period were identified, of which 25 (9.88%) underwent enucleation or evisceration. Risk factors for enucleation or evisceration included poor presenting visual acuity (OR 7.86, CI: 2.26, 27.3), high presenting intraocular pressure (OR 1.07, CI: 1.03, 1.12), presence of relative afferent pupillary defect (OR 3.69, CI: 1.20, 11.37) and positive vitreous culture for methicillin-resistant staphylococcus aureus (MRSA) (OR 18.3, CI: 1.54, 219.2) on multivariate analysis. Patients undergoing enucleation or evisceration were also more likely to have trauma, corneal ulcer or combined causes for endophthalmitis and underwent fewer salvaging surgical and procedural interventions. There were no significant differences in characteristics of those receiving enucleation versus evisceration in our cohort. CONCLUSION: Patients with endophthalmitis who underwent enucleation or evisceration had more severe disease on presentation compared to those treated with eye sparing therapy. Presenting clinical characteristics may have a role in triage and management decisions for patients presenting with severe endophthalmitis.

American Academy of Ophthalmology Recommendations on Screening for Endogenous Candida Endophthalmitis.

The American Academy of Ophthalmology evaluated the practice of routine screening for intraocular infection from Candida septicemia. In the United States, ophthalmologists are consulted in the hospital to screen for intraocular infection routinely for patients with Candida bloodstream infections. This practice was established in the era before the use of systemic antifungal medication and the establishment of definitions of ocular disease with candidemia. A recent systematic review found a rate of less than 1% of routinely screened patients with endophthalmitis from Candida septicemia. Other studies found higher rates of endophthalmitis but had limitations in terms of inaccuracies in ocular disease classification, lack of vitreous biopsies, selection biases, and lack of longer-term visual outcomes. Some studies attributed ocular findings to Candida infections, rather than other comorbidities. Studies also have not demonstrated differences in medical management that are modified for eye disease treatment; therefore, therapy should be dictated by the underlying Candida infection, rather than be tailored on the basis of ocular findings. In summary, the Academy does not recommend a routine ophthalmologic consultation after laboratory findings of systemic Candida septicemia, which appears to be a low-value practice. An ophthalmologic consultation is a reasonable practice for a patient with signs or symptoms suggestive of ocular infection regardless of Candida septicemia.

Characterizing the microbiota of instrumentation in ophthalmology clinics during and beyond the COVID-19 pandemic.

PURPOSE: Increased ophthalmology-specific risk of novel coronavirus 2019 (SARS-CoV-2) transmission is well-established, increasing the fear of infection and causing associated decreased rates of procedures known to save vision. However, the potential transmission from exposure to clinic instrumentation is unknown, including which additional pathogens may be spreading in this context. This study seeks to fill this gap by characterizing the microbiota of instrumentation in ophthalmology clinics during the COVID-19 pandemic and identifying potential sources of pathogenic spread encountered by patients and healthcare workers. METHODS: Thirty-three samples were captured using standard cultures and media. Ten positive and negative controls were used to confirm proper technique. Descriptive statistics were calculated for all samples. Samples were collected from the retina (N = 17), glaucoma (N = 6), cornea (N = 6), and resident (N = 4) clinics with rigorous disinfection standards at a tertiary academic medical center. Standard media cultures and/or polymerase chain reaction (PCR) was performed for each sample. RESULTS: From 33 samples, more than half (17/33, 51.5%) yielded bacterial growth. Using two different molecular methods, three samples (3/33, 9%) tested positive for SARS-CoV-2 (cycle thresholds 36.48, 37.14, and 37.83). There was no significant difference in bacterial growth (95% confidence interval [95% CI]: - 0.644-0.358, p = 0.076) among different clinics (retina, glaucoma, cornea, resident). Staphylococcus (S.) epidermidis grew most frequently (12/35, 34%), followed by S. capitis (7/35, 20%), Micrococcus luteus (2/35, 5.7%), Corynebacterium tuberculostearicum (2/35, 5.7%), and Cutibacterium ([C.], Propionibacterium) acnes (2/35, 5.7%). C. acnes growth was more frequent with imaging device forehead rests (2/7, 28.6%) than other surfaces (0/26, 0%, 95% CI: 0.019-0.619, p = 0.040). No samples isolated fungus or adenovirus. CONCLUSIONS: Most samples across subspecialty clinic instrumentation grew bacteria, and several tested positive for SARS-CoV-2. Many isolated pathogens have been implicated in causing infections such as endophthalmitis, conjunctivitis, uveitis, and keratitis. The clinical implications of the ophthalmology microbiome for transmitting nosocomial infections warrant optimization of disinfection practices, strategies for mitigating spread, and additional study beyond the pandemic.

GENESIS OF RETINAL-CHOROIDAL ANASTOMOSIS IN MACULAR TELANGIECTASIA TYPE 2: A Longitudinal Analysis.

PURPOSE: To longitudinally characterize structural/angiographic findings of retinal-choroidal anastomosis (RCA) in macular telangiectasia Type 2 (MacTel2). METHODS: A combined retrospective/prospective review of patients with MacTel2 with >2 visits and >2 months follow-up, including examination, fundus photography, fluorescein angiography, spectral-domain optical coherence tomography, and projection-resolved optical coherence tomography angiography. RESULTS: There were 24 eyes of 12 patients with a mean age of 61.1 (±7.3 [SD]) years and median follow-up of 447 (range 81-1,511) days. There were five eyes diagnosed with new RCA after not having any previously. Retinal-choroidal anastomosis was diagnosed in 8 (33%) eyes initially and eventually 13 (54%). In the eight eyes initially diagnosed with RCA, the number of RCAs and outer retinal hyperrflective lesions increased over the follow-up. The RCAs were found in clusters, generally temporal to the fovea. Retinal-choroidal anastomosis was uniformly associated with complete retinal subsidence, defined as the loss of outer nuclear layer substance such that the middle retinal layers sank down toward the retinal pigment epithelium (RPE), and was also present in each case. Each RCA colocalized with a region of hyperreflectivity, previously termed an outer retinal hyperreflective lesion. There was a lack of fluorescein leakage, lipid, hemorrhage, or any structural correlates with fluid exudation, and no signs of subretinal/subretinal pigment epithelium neovascularization. CONCLUSION: De novo RCA development seems to be associated with retinal subsidence, and after RCAs form, they increase in number and topographic distribution over time. Initially after formation, there was no sign of exudation. These data suggest the descent of the deep capillary plexus occurs with RCA, devoid of subretinal/subretinal pigment epithelium neovascularization in MacTel2.

Blunderbuss: Ocular and Orbital Injuries Due to Muzzle-Loading Firearms.

PURPOSE: Injury to the eye and/or orbital and adnexal structures associated with antiquated muzzle-loading firearms has not, to our knowledge, been characterized with the exception of a single case report. METHODS: A retrospective chart review of 7 patients treated at Vanderbilt University Medical Center from 2003 to 2017 who sustained traumatic injuries to the ocular and/or orbital structures secondary to the discharge of muzzle-loading firearms. The study was approved by the Vanderbilt Institutional Review Board. RESULTS: In 6/7 cases, injuries occurred secondary to the muzzle-loading firearm exploding due to dysfunction or misuse. Foreign material deriving from the firearm was retained in 3/7 patients. Initial examination of the orbit and adnexa revealed 5/7 individuals sustaining orbital fractures and 6/7 with facial lacerations (including 2 with eyelid lacerations); none had evidence of a lacrimal duct injury. Three patients suffered globe injuries (1 closed-globe and 2 open-globe). Visual acuity at last follow-up was ≥20/20 in 12/14 eyes examined. Surgical intervention was required in the treatment of 4/7 individuals (including 3/7 requiring intervention for sustained orbital fractures). No individuals were wearing eye protection at the time of injury. All individuals survived their injuries. CONCLUSIONS: The operation of muzzle-loading firearms poses a unique risk of injury to the operator. The resultant injuries in this case series were primarily due to the explosion of the firearm, which subsequently appear similar to orbital and ocular blast injuries caused by explosive weapons. Orbital injuries and more potentially more devastating ocular injuries may have been prevented by protective eyewear.

Novel REEP6 gene mutation associated with autosomal recessive retinitis pigmentosa.

PURPOSE: This study reports the ophthalmic and genetic findings of a Cameroonian patient with autosomal recessive retinitis pigmentosa (arRP) caused by a novel Receptor Expression Enhancing Protein 6 (REEP6) homozygous mutation. PATIENT AND METHODS: A 33-year-old man underwent comprehensive ophthalmic examinations, including visual acuity measurements, dilated fundus imaging, electroretinography (ERG), and spectral-domain optical coherence tomography (SD-OCT). Short-wavelength fundus autofluorescence (SW-AF) and near-infrared fundus autofluorescence (NIR-AF) were also evaluated. Whole exome sequencing (WES) was used to identify potential pathogenic variants. RESULTS: Fundus examination revealed typical RP findings with additional temporal ten micron yellow dots. SD-OCT imaging revealed cystoid macular edema and perifoveal outer retinal atrophy with centrally preserved inner segment ellipsoid zone (EZ) bands. Hyperreflective spots were seen in the inner retinal layers. On SW-AF images, a hypoautofluorescent area in the perifoveal area was observed. NIR-AF imaging revealed an irregularly shaped hyperautofluorescent ring. His visual acuity was mildly affected. ERG showed undetectable rod responses and intact cone responses. Genetic testing via WES revealed a novel homozygous mutation (c.295G>A, p.Glu99Lys) in the gene encoding REEP6, which is predicted to alter the charge in the transmembrane helix. CONCLUSIONS: This report is not only the first description of a Cameroonian patient with arRP associated with a REEP6 mutation, but also this particular genetic alteration. Substitution of p.Glu99Lys in REEP6 likely disrupts the interactions between REEP6 and the ER membrane. NIR-AF imaging may be particularly useful for assessing functional photoreceptor cells and show an "avocado" pattern of hyperautofluorescence in patients with the REEP6 mutation.

Linear and planar reflection artifacts on swept-source and spectral-domain optical coherence tomography due to hyperreflective crystalline deposits.

PURPOSE: To describe novel spectral-domain (SD) and swept-source (SS) optical coherence tomography (OCT) linear and planar reflection artifacts produced by hyperreflective crystalline deposits (HCD). METHODS: Imaging from 10 eyes with HCD producing linear and planar artifacts on OCT was retrospectively analyzed. All eyes had SD-OCT (Spectralis HRA + OCT, Heidelberg Engineering, Germany) and SS-OCT angiography (PLEX Elite 9000, Carl Zeiss Meditec, Inc., Dublin, CA) acquired on the same day. The horizontal extent of planar artifacts and the corresponding HCD on B-scans was measured using a digital caliper. Artifact features from HCD in eyes with non-neovascular age-related macular degeneration (AMD) were analyzed and compared to those seen in two eyes with the "onion sign," an OCT signature previously shown to represent cholesterol crystals (CC) in the sub-retinal pigment epithelium-basal laminar space of eyes with neovascular AMD. A third eye with the "onion sign" was imaged with dense B-scan (DB)-OCTA. RESULTS: Ten eyes of ten patients (77.4 ± 8.7 years) with HCD were analyzed. On SS-OCTA, HCD produced linear artifacts of high signal intensity passing through the HCD and spanning the entire scan depth. On SD-OCT, HCD produced planar artifacts located anterior to both the retina and a hyporeflective space representing normal vitreous signal. The horizontal extent of the artifact did not differ significantly from the corresponding HCD on OCT B-scans (P = 0.62). The OCT artifacts produced by the "onion sign" appeared similar to those of HCD. The additional eye with neovascular AMD imaged with DB-OCTA was characterized by a single, vertical, linear false-flow signal crossing retinal layers. CONCLUSIONS: To the authors' knowledge, this is the first description of SD- and SS-OCT/OCTA artifacts corresponding to both HCD and the "onion sign." These artifacts are likely due to highly reflective CC previously shown on histology to correspond to both of these OCT signatures.

CHARACTERIZING RETINAL-CHOROIDAL ANASTOMOSIS IN MACULAR TELANGIECTASIA TYPE 2 WITH OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To characterize structural and angiographic findings in macular telangiectasia Type 2 (MacTel 2) and examine associations with visual acuity. METHODS: MacTel 2 patients with complete ophthalmologic examination, including fundus photography, autofluorescence, spectral-domain optical coherence tomography, and projection-resolved optical coherence tomography angiography, were retrospectively evaluated. RESULTS: There were 43 eyes of 22 patients with a mean age 63.9 (±10.3) years. Six patients had diabetes. Twenty-one eyes (48.8%) had retinal-choroidal anastomoses (RCAs) without any evidence of neovascularization extending laterally in a plane above or below the retinal pigment epithelium. None of the eyes had hemorrhage, lipid, or signs of subretinal exudation. When present, an average of 55 (±33.7) individual RCAs were clustered primarily in temporal juxtafoveal region of involved eyes. Right-angle veins were seen in all 21 eyes with RCAs, and hyperpigmentation was present in 18 (P < 0.001 for both). A conical collection of hyperreflective material spanning from Bruch membrane past external limiting membrane of ≥200-µm basal diameter was found in 21 eyes and labeled outer retinal hyperreflective lesion. Retinal-choroidal anastomoses occurred in clusters, often within the outer retinal hyperreflective lesion. This lesion colocalized with focal thinning of the outer nuclear layer and was surrounded by a larger defect in the ellipsoid zone. The presence of diabetes (P = 0.015), outer retinal hyperreflective lesion (P = 0.006), RCA (P = 0.005), and ellipsoid zone defect extent (P < 0.001) were associated with decreased visual acuity. CONCLUSION: Retinal-choroidal anastomoses occur in eyes with MacTel 2 without signs of exudation. Retinal-choroidal anastomoses occur in numerous clusters particularly in the temporal juxtafoveal macula. Diabetes, ellipsoid zone defect extent, RCAs, and the outer retinal hyperreflective lesion predict poorer vision in MacTel 2.

Choroidal origin of endogenous Candida endophthalmitis.

Endogenous Candida endophthalmitis (ECE) has been established with microscopic histopathology, both by autopsy and experimentation, to primarily originate from and involve the choroid. Zhuang et al. examined a series of patients with ECE using spectral-domain optical coherence tomography (SD-OCT) imaging and present a new classification scheme. The authors conclude the majority of lesions are primarily retinal in location without report of choroidal involvement. This discrepancy may be explained by posterior shadowing artifact and lack of discernment from associated retinal findings like infarction. These considerations are necessary in reviewing SD-OCT, characterizing ECE, and proposing new classification systems.

Oculomotor Synkinesis (Aberrant Reinnervation of the Third Cranial Nerve) Associated with Atypical Tolosa-Hunt Syndrome.

A 70-year-old woman with systemic lupus erythematosus developed a painful pupil-involving right third nerve palsy, ipsilateral fourth nerve palsy, and periorbital paraesthesia. Magnetic resonance imaging demonstrated enhancement and thickening of the right third nerve, and she was diagnosed with presumed Tolosa-Hunt syndrome. Repeated imaging seven months later showed resolution of the enhancing thickened oculomotor nerve, but the patient developed signs of oculomotor synkinesis. This presentation demonstrates a rare case of oculomotor synkinesis secondary to inflammation.

Novel FOXC2 Mutation and Distichiasis in a Patient With Lymphedema-Distichiasis Syndrome.

A 4 year-old-boy was referred for distichiasis of the upper and lower lids of both eyes that had been present since at least 1 year of age. The patient's family history was notable for distichiasis and lymphedema affecting numerous family members. The patient was found to have a novel heterozygous variant (c.741_742insGG) in the FOXC2 gene. Mutations in the FOXC2 gene are associated with lymphedema-distichiasis syndrome. An important feature of lymphedema-distichiasis syndrome is that distichiasis is typically present prior to the onset of lymphedema.

Remote orbital recurrence of olfactory neuroblastoma (esthesioneuroblastoma).

Olfactory neuroblastoma is a rare and often locally aggressive malignancy that invades the orbit via local destruction. It is known to recur in a delayed fashion, particularly to the neck lymph nodes. This is a case of a 65-year-old gentleman who presents with recurrence in the orbit and a neck lymph node 19 years after treatment for his initial disease. This report describes the longest known interval in orbital recurrence and should alert the monitoring physician that extreme delays in recurrence can occur.