Quantitative fundus autofluorescence in smokers compared to non-smokers.

Increased fundus autofluorescence is directly related to increased RPE lipofuscin deposition in the retina and has been observed in eyes with age-related macular degeneration (AMD). Smoking is the most significant modifiable risk factor for the development and progression of AMD, in which one of the main mechanisms is oxidative damage from smoking leading to RPE cell toxicity. The relationship between smoking and autofluorescence is not established and could provide insight into pathogenic mechanism of AMD. Therefore, our objective was to compare quantitative fundus autofluorescence (qAF) in the retinae of healthy non-smokers to smokers. We conducted a cross-sectional study at the 2016 Minnesota State Fair. Participants self-reported past medical and ocular history and underwent eye examination as well as qAF imaging with Spectralis confocal scanning laser ophthalmoscope (cSLO) equipped with an internal fluorescent reference. Two sets of images were obtained per eye. Stepwise multiple mixed effects regression model was used to examine the relationship between mean qAF values and smoking status. We enrolled 105 individuals (54 smokers, 61 females, mean age 41 years with range 18-78 years old). Fundus autofluorescence images were analyzable for 85 of 105 individuals contributing 161 eyes (80 right, 81 left). The repeatability coefficients between the first set and second set of images were ±21% of their mean qAF values. Older age and female gender were independently associated with higher qAF. Positive smoking history tended to result in higher qAF values after adjusting for age and gender but was not statistically significant (0.118, 95%CI -0.003, 0.240, P = 0.056). Among smokers, the number of pack-years smoked was not significantly associated with higher qAF. Our study's results are consistent with existing literature in which older age is predictive of intensified autofluorescence, while smoking history does not have as important of an impact on autofluorescence as hypothesized. Several large epidemiological studies have shown that smoking is significantly associated with AMD, and qAF is likely not the appropriate modality to clinically assess smoking's impact on retinae.

Observing the initial onset of retinal vasculitis as unilateral Birdshot Retinochoroiditis becomes bilateral: A case report.

Purpose: Birdshot Retinochoroiditis (BRC) is an uncommon but distinct form of bilateral posterior uveitis. It is generally of indolent onset, making early natural history difficult to study. Our report seeks to expand knowledge on the natural history of the onset of BRC. Observations: Our patient presented with clinical features that were consistent with unilateral BRC, despite it being defined as a bilateral condition. Over the course of one year he developed retinal vasculitis, vitritis and fundus features of BRC in the second eye. Conclusions and Importance: Although BRC is a bilateral disease, our case demonstrates that the onset may sometimes be sequential instead of simultaneous. Unilateral disease that is characteristic of BRC should be monitored for second-eye involvement with multi-modal imaging including fundus photography, angiography, perimetry, electroretinography, and optical coherence tomography of the macula with emphasis on the choroidal thickness.

Paraneoplastic Conjunctival Acanthosis Nigricans: A Case Report.

PURPOSE: To report a patient who presented with red eye and diffuse palpebral conjunctival thickening and papillary growth bilaterally. METHODS: A 63-year-old woman with a medical history of stage IV adenocarcinoma of the lung with metastasis to the bone, the lung, and the lymph nodes presented with redness and irritation of both eyes for 3 months. The patient has been treated with topical corticosteroids for 3 weeks with no relief of symptoms. RESULTS: Clinical examination and pathology report of conjunctival biopsy confirmed the diagnosis of conjunctival acanthosis nigricans. CONCLUSIONS: Conjunctival acanthosis nigricans is a rare paraneoplastic condition that resembles papilloma and can present a challenge in diagnosis. When acanthosis nigricans occurs after the diagnosis of malignancy, it can be an indicator of progression of the underlying condition. The diagnosis of conjunctival acanthosis nigricans in a patient with no history of cancer should prompt clinicians for further malignancy workup.

Lichen simplex chronicus of the eyelid: A case report and literature review.

PURPOSE: To report a case of lichen simplex chronicus (LSC) of the eyelid and to perform a literature review on this topic. OBSERVATIONS: A 59-year-old African American man presents with chronic and recalcitrant recurrent chalazion of both upper eyelids despite aggressive medical management. An incision and drainage procedure was performed along with biopsy of the eyelid, which was found to be consistent with LSC. A thorough review of the English literature pertaining to LSC of the eyelids was performed by querying PubMed and Google Scholar. Though two clinical reports of LSC of the eyelid were found in older literature, only one such case confirmed by biopsy has been reported until now. CONCLUSIONS: LSC of the eyelid is rare and this is the first reported case that is associated with chronic and recalcitrant chalazion.

Incidence, Management, and Surgical Outcomes of Macular Splitting Rhegmatogenous Retinal Detachment.

BACKGROUND AND OBJECTIVE: Limited knowledge exists regarding macular splitting retinal detachment (RD). The purpose of this study is to investigate clinical features and outcomes of macular splitting RD. PATIENTS AND METHODS: This was a retrospective case series performed at a single practice. Macular splitting RD was identified clinically and on optical coherence tomography (OCT). Primary outcomes were anatomical and functional success, and secondary outcomes were factors associated with postoperative visual acuity. RESULTS: The overall number of patients with OCT-confirmed macular splitting RD was 16 of 664, which is an incidence rate of 2.4%. Preoperative and final logMAR were 0.33 and 0.13, respectively (P = .002). Presenting visual acuity (VA) (P = 0.015) and duration of symptoms (P = .007) were associated with final VA, whereas time to surgery was not significant (P = .581). CONCLUSION: The incidence of macular splitting RD is higher than previously reported. Anatomical and functional outcomes were excellent in this study. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:602-608.].

Pars Plana Vitrectomy Outcomes for Rhegmatogenous Retinal Detachment Qualifying for Pneumatic Retinopexy.

PURPOSE: To investigate real-world outcomes of pars plana vitrectomy (PPV) for eyes with primary rhegmatogenous retinal detachments (RRD) eligible for pneumatic retinopexy (PnR). METHODS: This was a single center retrospective case series looking at consecutive patients with primary RRDs. A database was created on all patients with a primary RRD from 2010 to 2018 based on billing code 67108. Eyes anatomically eligible for PnR were reviewed for preoperative, intraoperative and postoperative characteristics. The main outcome assessed was single surgery anatomical success (SSAS), final anatomical success (FAS), and postoperative LogMAR vision. RESULTS: A total of 720 eyes (age, 62.9 ± 9.1 years; 61.7% were male) met inclusion criteria for PnR and underwent PPV. SSAS was 94.0% and FAS was 99.9%. Preoperative and final LogMAR vision was 0.853 and 0.293 (P<0.001) in eyes with SSAS vs 0.714 and 0.648 (P=0.686) in eyes with primary failure. PVR was the most common etiology of primary surgical failure (n=21, 49%). Patients who failed primary repair had a mean of 1.12 additional surgeries with a median time of 45 days between surgeries. CONCLUSION: A robust single surgery success rate with good visual outcomes was achieved across 8 years and multiple surgeons utilizing PPV to treat primary RRDs in eyes which anatomically qualified for pneumatic retinopexy in a real-world setting.

Comparing fundus autofluorescence and infrared imaging findings of peripheral retinoschisis, schisis detachment, and retinal detachment.

PURPOSE: The primary goal of this study was to identify characteristic features of peripheral degenerative retinoschisis (RS), schisis detachment (SD) and retinal detachment (RD) on both fundus autofluorescence (FAF) and infrared (IR) imaging, using spectral domain optical coherence tomography (SD-OCT) imaging of the peripheral retina as the confirmatory imaging tool. METHODS: This is a descriptive case series study. A total of 27 eyes of 22 patients were included. Thirteen eyes of 10 patients diagnosed with RS, 4 eyes of 3 patients diagnosed with SD, and 10 eyes of 9 patients diagnosed with RD were included. Patients with images of poor quality were excluded. Heidelberg Spectralis HRA + OCT machine (Heidelberg Engineering, Heidelberg, Germany) were used to acquire the images. RESULTS: All conditions appeared as areas of hypo-AF on FAF and hypo-reflectance on IR imaging. Accentuated vasculature of the lesion was noted with IR imaging due to elevation of the RS and RD, which was less frequently observed with FAF. On FAF, a hyper-AF leading edge around the RS lesion indicated the presence of intraretinal or subretinal fluid and an extension of the RS. Retinal breaks/holes were best visualized with IR imaging. SD-OCT confirmed the diagnosis in all performed cases. CONCLUSIONS: We were unable to differentiate between RS and RD based solely on findings from FAF and IR imaging. However, the combination of them with SD-OCT can assist in the diagnosis of RS from RD and in the evaluation of RS progression. OCT remains the main modality imaging to differentiate these conditions.

Trade-Off Between Field-of-View and Resolution in the Thermal-Integrated Argus II System.

PURPOSE: To investigate the effect of a wider field-of-view (FOV) of a retinal prosthesis on the users' performance in locating objects. METHODS: One female and four male subjects who were blind due to end-stage retinitis pigmentosa and had been implanted with the Argus II retinal prosthesis participated (aged 63.4 ± 15.4). Thermal imaging was captured by an external sensor and converted to electrical stimulation to the retina. Subjects were asked to localize and to reach for heat-emitting objects using two different FOV mappings: a normal 1:1 mapping (no zoom) that provided 18° × 11° FOV and a 3:1 mapping (zoom out) that provided 49° × 35° FOV. Their accuracy and response time were recorded. RESULTS: Subjects were less accurate and took longer to complete the tasks with zoom out compared to no zoom. Localization accuracy decreased from 83% (95% confidence interval, 75%, 90%) with no zoom to 76% (67%, 83%) with zoom out (P = 0.07). Reaching accuracy differed between the two mappings only in one subject. Response time increased by 43% for the localization task (24%, 66%; P < 0.001) and by 20% for the reaching task (0%, 45%; P = 0.055). CONCLUSIONS: Argus II wearers can efficiently find heat-emitting objects with the default 18° × 11° FOV of the current Argus II. For spatial localization, a higher spatial resolution may be preferred over a wider FOV. TRANSLATIONAL RELEVANCE: Understanding the trade-off between FOV and spatial resolution in retinal prosthesis users can guide device optimization.

Characterization of Epiretinal Proliferation in Full-Thickness Macular Holes and Effects on Surgical Outcomes.

PURPOSE: Epiretinal proliferation is a distinct clinical entity from epiretinal membrane that classically is associated with lamellar macular holes, but its prevalence and association with full-thickness macular holes (FTMH) have not been well described. We characterized macular hole-associated epiretinal proliferation (MHEP) and its effects on long-term surgical outcomes. DESIGN: Multicenter, interventional, retrospective case-control study. PARTICIPANTS: Consecutive eyes that underwent surgery for FTMH with a minimum of 12 months follow-up. METHODS: All eyes underwent pars plana vitrectomy, removal of any epiretinal membranes, and gas tamponade, with or without internal limiting membrane (ILM) peeling. Spectral-domain OCT imaging was obtained before and after surgery. MAIN OUTCOME MEASURES: Improvement in visual acuity and single-surgery hole closure rates in eyes with, versus without, MHEP at 12 months. RESULTS: Seven hundred twenty-five charts were analyzed, and 113 patients met inclusion criteria. Of 113 eyes with FTMH, 30 (26.5%) showed MHEP. Patients with FTMH and MHEP were older (P < 0.002) and more often men (P = 0.001), and showed more advanced macular hole stages than those without MHEP (P = 0.010). A full posterior vitreous detachment was more common in eyes with MHEP (P < 0.004). Twelve months after surgery, FTMH with MHEP patients showed significantly less improvement in visual acuity (P = 0.019) with higher rates of ellipsoid and external limiting membrane defects (P < 0.05) and with a higher rate of failure to close with 1 surgery compared to FTMH without MHEP (26.7% vs. 4.8%; P = 0.002]). Peeling the ILM was associated with improved rates of hole closure in FTMH with MHEP (P < 0.001). Multivariate testing confirmed that the presence of MHEP was an independent risk factor for less visual improvement (P = 0.031) and for single-surgery nonclosure (P = 0.009) and that ILM peeling improved single-surgery closure rates (P = 0.026). CONCLUSIONS: We found that FTMH with MHEP showed poorer anatomic and visual outcomes after vitrectomy compared with FTMH without MHEP. Internal limiting membrane peeling was associated with improved closure rates and should be considered when MHEP is detected before surgery.

Orbital Paraganglioma: A Systematic Review.

Purpose The purpose of this study was to perform a systematic review of the literature on orbital paragangliomas, evaluating clinical presentation, diagnosis, management patterns, and prognosis. Methods The systematic review was conducted based on the principles described in the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. PubMed, Cochrane databases, Embase, and Web of Science were searched for articles related to orbital paragangliomas. Inclusion criteria included English language articles with original reports on human subjects. Data on clinical presentation, diagnosis, treatment, and prognosis were collected. Results Twenty-seven articles met inclusion criteria (28 total patients). The mean patient age was 37.1 years (range, 3-75 years); 13 (46.4%) patients were male. The most common presenting symptoms were proptosis (89.2%), visual acuity changes (67.9%), and extraocular muscle restriction (64.2%). Lesions were most commonly intraconal (92.9%). Single modality therapy was employed in 19 patients (67.9%), including excision in 12 patients (42.9%) and exenteration in 5 patients (17.9%). Ten patients (35.7%) developed recurrence, and there was a 92.9% survival rate (mean follow-up, 29 months). Conclusion Orbital paragangliomas are rare tumors with an excellent prognosis. These lesions commonly present with proptosis, and are primarily managed surgically with simple excision, although exenteration and adjuvant radiation may be necessary for invasive tumors. This series is the largest and most comprehensive systematic review of orbital paragangliomas conducted to date.

Ruptured Retinal Arterial Macroaneurysm Secondary to Toxoplasmic Kyrieleis Arteriolitis: A Case Report.

PURPOSE: The aim of this report was to describe multimodal ocular imaging findings in a patient who presented with a ruptured retinal arterial macroaneurysm (RAM) associated with toxoplasmic Kyrieleis arteriolitis. METHODS: We report the case of a 64-year-old man with a history of systemic hypertension and dense amblyopia of the left eye who presented with decreased vision and new floaters in the left eye. Color fundus photography, spectral-domain optical coherence tomography, fluorescein angiography, and indocyanine green angiography were used as diagnostic imaging tools. RESULTS: No signs of hypertensive retinopathy were noted in the right eye. Multiple chorioretinal scars characteristic of previous toxoplasmosis were revealed in the left eye, with one covering most of the macula. Periarterial plaques or Kyrieleis arteriolitis were observed in retinal arteries surrounding the toxoplasmic retinal scars. Multiple RAMs were observed in these vessels, one of which was acutely ruptured. A perivenular plaque associated with a chronic branch retinal vein occlusion (BRVO) was noted along the same arcade at the arteriovenous crossing. CONCLUSION: RAM formation and BRVO can present as possible long-term complications of toxoplasmic Kyrieleis arteriolitis. This is the first reported case demonstrating an association between toxoplasmic Kyrieleis arteriolitis and RAM formation.

Antibody-mediated Hsp70 protein therapy.

Intracellular Hsp70 provides cytoprotection against a variety of stressful stimuli, and an effective means of increasing intracellular Hsp70 levels could prove beneficial in the prevention and treatment of a variety of human diseases. A novel protein transduction domain consisting of the single chain Fv fragment of an anti-DNA antibody known to penetrate into living cells and tissues, mAb 3E10, has recently been used to deliver functional proteins to cells. The ability of the single chain Fv fragment to deliver Hsp70 into living cells was tested by generating an Fv-Hsp70 fusion protein. Fv-Hsp70 was produced as a secreted protein in both COS-7 cells and the methylotropic yeast strain Pichia pastoris and was shown capable of penetrating into COS-7 cells and primary rat cortical neurons. Pre-treatment with Fv-Hsp70 protected both COS-7 cells and primary rat cortical neurons against subsequent exposure to hydrogen peroxide. These results provide the first evidence that the Fv fragment of mAb 3E10 is capable of delivering proteins to neurons and indicate its potential in the development of Hsp70 protein therapy.

Spectral-Domain Optical Coherence Tomography in Older Patients With History of Retinopathy of Prematurity.

BACKGROUND AND OBJECTIVE: To characterize the in vivo microstructural features of patients with history of retinopathy of prematurity (ROP). PATIENTS AND METHODS: A single-center, retrospective imaging case series during which a chart review was performed of consecutive patients with history of ROP who underwent spectral-domain optical coherence tomography (SD-OCT) with or without enhanced depth imaging. Eyes with time-domain OCT, no light perception, or uninterpretable SD-OCT images were excluded. Main outcome measures included best-corrected visual acuity (BCVA) and exploratory SD-OCT findings. RESULTS: A total of 186 eyes of 112 patients (mean age: 31.5 years; range: 8 years to 70 years) were imaged. Mean visual acuity was 20/150 (range: 20/20 to light perception). Mean foveal thickness (MFT) and subfoveal choroidal thickness (SCT) measured 270.93 µm ± 56.40 µm and 239.87 µm ± 73.00 µm, respectively. There was a negative correlation between ROP stage and MFT (Rho = -0.19; P = .027), but not with SCT (Rho = -0.03; P = .748). There were negative correlations between BCVA and MFT (Rho = -0.23; P < .01) and SCT (Rho = -0.19; P = .04). Ellipsoid zone (EZ) abnormalities, inner retinal layer thickening, and presence of chorioretinal atrophy were associated with higher ROP stage (P < .001) and poorer visual acuity (Rho = 0.59; P < .001). The presence of retinoschisis (n = 36/186; 19%) was associated with poorer visual acuity (P < .001), but did not correlate with higher ROP stage (P = .17). Epiretinal membrane-like dense hyaloidal organization and vitreoretinal interface abnormalities were seen in 69% (130/186) and 33% (63/186) of eyes, respectively, but were not associated with ROP stage (P = .87) or visual acuity (P = .54). After controlling for EZ abnormalities, foveal hypoplasia, macular schisis, inner retinal thickening, chorioretinal atrophy, and ROP stage, the independent risk factors for poorer visual acuity were EZ abnormalities (Beta = 0.38; P < .001), chorioretinal atrophy (Beta = 0.18; P = .03), and ROP stage (Beta = 0.22; P < .01). CONCLUSION: SD-OCT imaging identified a variety of microstructural abnormalities present in patients with history of ROP. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:1086-1094.].

Autoimmune inner ear disease in children.

OBJECTIVE: To determine the response to treatment of pediatric patients diagnosed with autoimmune inner ear disease. PATIENTS: Seven children who presented with sensorineural hearing loss and were diagnosed with autoimmune inner ear disease. INTERVENTION: Diagnosis through blood testing. Treatment with steroids and/or cytotoxic medication. MAIN OUTCOME MEASURES: Improvement in pure-tone average and speech discrimination scores on audiometric testing. RESULTS: Six of the 7 children (85.7%) improved with treatment, and the remaining patient had no measurable progression of disease. CONCLUSION: Children with autoimmune inner ear disease seem to benefit from treatment with steroids and/or cytotoxic medication. Although such medications must be used with caution in the pediatric population, they should not be withheld simply because of young age.

Effects of cystic fibrosis transmembrane conductance regulator and DeltaF508CFTR on inflammatory response, ER stress, and Ca2+ of airway epithelia.

We tested whether cystic fibrosis (CF) airway epithelia have larger innate immune responses than non-CF or cystic fibrosis transmembrane conductance regulator (CFTR)-corrected cells, perhaps resulting from ER stress due to retention of DeltaF508CFTR in the endoplasmic reticulum (ER) and activation of cytosolic Ca(2+) (Ca(i)) and nuclear factor (NF)-kappaB signaling. Adenovirus infections of a human CF (DeltaF508/DeltaF508) nasal cell line (CF15) provided isogenic comparisons of wild-type (wt) CFTR and DeltaF508CFTR. In the absence of bacteria, there were no or only small differences among CF15, CF15-lacZ (beta-galactosidase-expressing), CF15-wtCFTR (wtCFTR-corrected), and CF15-DeltaF508CFTR (to test ER retention of DeltaF508CFTR) cells in NF-kappaB activity, interleukin (IL)-8 secretion, Ca(i) responses, and ER stress. Non-CF and CF primary cultures of human bronchial epithelial cells (HBE) secreted IL-8 equivalently. Upon infection with Pseudomonas aeruginosa (PA) or flagellin (key activator for airway epithelia), CF15, CF15-lacZ, CF15-wtCFTR, and CF15DeltaF508CFTR cells exhibited equal PA binding, NF-kappaB activity, and IL-8 secretion; cells also responded similarly to flagellin when both CFTR (forskolin) and Ca(i) signaling (ATP) were activated. CF and non-CF HBE responded similarly to flagellin + ATP. Thapsigargin (Tg, releases ER Ca(2+)) increased flagellin-stimulated NF-kappaB and ER stress similarly in all cells. We conclude that ER stress, Ca(i), and NF-kappaB signaling and IL-8 secretion were unaffected by wt- or DeltaF508CFTR in control and during exposure to PA, flagellin, flagellin + ATP, or flagellin + ATP + forskolin. Tg, but not wt- or DeltaF508CFTR, triggered ER stress. Previous measurements showing hyperinflammatory responses in CF airway epithelia may have resulted from cell-specific, rather than CFTR- or DeltaF508CFTR-specific effects.