Metastatic papillary renal cell carcinoma to the retina and vitreous.

Purpose: To describe the presentation, evaluation, and management of vitreoretinal metastasis from papillary renal cell carcinoma. Observations: A 53-year-old woman presented with a six-week history of dark floaters in the right eye. Vitreous veils and white pre-retinal plaques were identified in the posterior pole and extended to a temporal peripheral lesion suggestive of retinal infiltration. Optical coherence tomography revealed clumps of pre-retinal hyper-reflective material in the macula and a large hyper-reflective plaque-like lesion involving the internal limiting membrane in the temporal periphery. Fluorescein angiography demonstrated patchy hyperfluorescence with mild leakage at the temporal lesion and there was no evidence of choroidal involvement on indocyanine green angiography. Vitreoretinal biopsy confirmed the diagnosis of metastatic papillary renal cell carcinoma which spurred further systemic metastatic evaluation. Choroidal metastasis developed 15 months later in the fellow eye highlighting different types of intraocular metastatic spread in the same patient. Conclusions and Importance: This case report illustrates a rare presentation of papillary renal cell carcinoma with metastasis to the retina and vitreous. Ophthalmologists should be aware of the appearance and imaging characteristics of retinal and vitreous metastases, which can be the first presentation of a new or newly metastatic malignancy. These lesions can resemble infectious or inflammatory mimickers and may require biopsy to secure the diagnosis and to guide vision- and life-preserving treatment.

Ultra-Widefield Imaging of Presumed Vitreous Base-Associated Vasculopathy: Assessment of Peripheral Retinal Hemorrhages and Microaneurysms.

Purpose: To describe cases of asymptomatic peripheral retinal hemorrhage attributed to presumed vitreous base traction seen on ultra-widefield (UWF) imaging. Methods: This retrospective consecutive series comprised asymptomatic patients with peripheral retinal hemorrhages, microaneurysms, or both. Imaging included UWF fundus photography, fundus autofluorescence, fluorescein angiography (FA), optical coherence tomography (OCT), or a combination. Results: The series included 9 adult patients. The findings were observed on a routine eye examination or as an incidental finding in the contralateral eye of patients presenting with a retinal break or detachment. On UWF imaging, the distinguishing features of the peripheral retinal hemorrhages and microaneurysms presumably caused by vitreous base traction were their pinpoint shape and location at the vitreous base, in particular in the far temporal and superior retinal periphery. UWF FA showed punctate hyperfluorescent spots with no leakage. OCT showed signs of evolving posterior vitreous detachment. Management was limited to observation; with time, the microaneurysms were stable and the hemorrhages resolved. Conclusions: UWF imaging has led to the identification of presumed vitreous base vasculopathy. After a targeted workup is unrevealing, observation is appropriate.

Diurnal variation of optical coherence tomography-based macular fluid in exudative age-related macular degeneration.

BACKGROUND: Significant diurnal fluctuation of optical coherence tomography (OCT)-based macular fluid occurs in patients with several macular conditions including diabetic macular edema (DME) and cystoid macular edema due to retinal venous occlusion (RVO). OCT imaging and analysis of macular fluid status plays a central role in clinical management of exudative age-related macular degeneration (eAMD), however diurnal variation of eAMD OCT findings has not yet been formally studied. Herein, we investigate whether clinically meaningful fluctuation of OCT-based macular fluid occurs in patients with eAMD. METHODS: Prospective observational study. Patients with eAMD and intra- and/or sub-retinal fluid on early AM OCT were enrolled to receive two consecutive OCT scans at least four hours later. Retinal layers were manually segmented on all OCT rasters and AM-to-PM and PM-to-PM image pairs were analyzed for total retinal and neurosensory retinal volume changes within the central 1 and 3 mm ETDRS subfields. Finally, two masked retinal specialists analyzed all OCT image pairs for qualitative differences that may impact clinical management. RESULTS: 21 patients with eAMD and fluid on OCT were recruited between January 2020 and November 2021. There was no mean difference between AM and PM central 3 mm total retinal volume (p = 0.56), central 3 mm neurosensory retinal volume (p = 0.25), central 1 mm total retinal mean thickness (p = 0.96), or central 1 mm neurosensory retinal mean thickness (p = 0.63), nor were any differences identified in PM-to-PM control comparisons. Qualitative analysis by two masked experts identified no clinically significant differences between any AM-to-PM OCT image pairs. CONCLUSIONS: No significant diurnal variation in OCT-based macular fluid or thickness was identified in patients with eAMD, either quantitatively or qualitatively.

Controversies and Disparities in the Management of Age-Related Macular Degeneration.

Age-related macular degeneration is a leading cause of blindness in patients aged 50 years and older. Prior to the 21st century, there were no effective treatments for this devastating disease. However, the last 20 years have heralded the development of treatments for both the nonexudative and exudative forms. The invention of AREDS vitamin supplements and anti-VEGF therapies forever changed the treatment of dry and wet age-related macular degeneration, respectively. The rapid adoption and expansion of these vision preserving treatments has created controversy regarding their cost, burden of administration, development, and use of new technologies, genetic considerations, and observed societal disparities. Many of these controversies and disparities persist today and will require further research to resolve.

Telemedicine for Preoperative Evaluation of Upper Eyelid Malposition: Reliability of Diagnosis and Surgical Plan.

PURPOSE: Outpatient visits and surgeries for nonurgent indications in ophthalmology have intermittently been restricted during the COVID-19 pandemic. Telemedicine services have rapidly gained acceptance during this period, and could improve patient access for routine oculoplastic evaluations in the future. The objective of this study is to investigate interobserver and intraobserver reliability of eyelid and brow position assessment and surgical plan when comparing photography-based and face-to-face evaluation. METHODS: This was an observational study conducted at a single academic center. Thirty randomly selected patients who had completed an in-office evaluation for chief complaint of "drooping eyelids" between June 2019 and March 2020 were included. Virtual assessment of brow position, dermatochalasis, blepharoptosis, and margin-reflex distance 1 was performed by 2 oculoplastic surgeons based on external photographs, and a surgical plan was formulated. Fraction of agreement and Cohen's κ were determined to evaluate reliability of the virtual assessment compared to face-to-face examination. RESULTS: For 60 eyes from 30 study subjects, diagnostic reliability for observer A was near perfect for brow ptosis, substantial for blepharoptosis and moderate for dermatochalasis (κ = 0.86, 0.67, and 0.57, respectively); for observer B, reliability was moderate for brow and blepharoptosis and substantial for dermatochalasis (0.47, 0.59, and 0.79). Fraction of agreement for blepharoptosis was 94% in eyes where the eyelid margin was visible, and 66% in eyes where the eyelid margin was obscured by overhanging skin. Virtual margin-reflex distance 1 measurements were highly correlated with those obtained face to face (r = 0.77, p < 0.01). Fraction of agreement for surgical plan after virtual examination by observer A/B, respectively, was 100%/94% for brow lift, 90%/87% for blepharoptosis repair and 83%/83% for functional upper blepharoplasty. CONCLUSIONS: Virtual evaluation of upper eyelid and brow malposition can be performed with acceptable reliability. Co-existing dermatochalasis or brow ptosis may require special photographic technique or video examination to ensure an appropriate diagnosis. A photography-based preliminary surgical plan offers a viable alternative to face-to-face encounters.

OS reboot.

Cerebrospinal fluid (CSF) diversion or shunting procedures are the most commonly performed surgery for the treatment of hydrocephalus and are often employed in the management of elevated intracranial pressure due to a variety of diseases. Despite their popularity however, approximately 50% of shunts fail within the first two years, and several revisions are required within the first decade after placement. Ophthalmologists may encounter patients with a CSF shunt to evaluate for concerns of vision loss or diplopia and to determine if papilledema is present. We discuss the neuro-ophthalmic manifestations and evaluation of possible CSF shunt malfunction.

Automated detection of squint as a sensitive assay of sex-dependent calcitonin gene-related peptide and amylin-induced pain in mice.

ABSTRACT: We developed an automated squint assay using both black C57BL/6J and white CD1 mice to measure the interpalpebral fissure area between the upper and lower eyelids as an objective quantification of pain. The automated software detected a squint response to the commonly used nociceptive stimulus formalin in C57BL/6J mice. After this validation, we used the automated assay to detect a dose-dependent squint response to a migraine trigger, the neuropeptide calcitonin gene-related peptide, including a response in female mice at a dose below detection by the manual grimace scale. Finally, we found that the calcitonin gene-related peptide amylin induced squinting behavior in female mice, but not males. These data demonstrate that an automated squint assay can be used as an objective, real-time, continuous-scale measure of pain that provides higher precision and real-time analysis compared with manual grimace assessments.

PERSISTENT PLACOID MACULOPATHY-LIKE FINDINGS IN PATIENTS WITH GIANT CELL ARTERITIS.

PURPOSE: To describe two patients with giant cell arteritis who presented with macular lesions mimicking persistent placoid maculopathy. METHODS: Retrospective case reports. PATIENT: Two patients, a 74-year-old man and an 85-year-old woman both were diagnosed with biopsy-confirmed giant cell arteritis with vision loss in one eye due to arteritic ischemic optic neuropathy. Both presented many years later with acute vision loss in the remaining eye. RESULTS: Both patients had bilateral retinal whitening in the parafovea, and the second also had sectoral optic disk swelling. On fluorescein angiography, these areas of retinal whitening in both patients were hypofluorescent early with late hyperfluorescence staining. On indocyanine green angiography, there were areas of foveal hypocyanescence bilaterally in both patients that persisted throughout the imaging and were more apparent late. These findings can be seen in patients with bilateral persistent placoid maculopathy. CONCLUSION: Giant cell arteritis should be included in the differential diagnosis of persistent placoid maculopathy.

A Population-Based Study of Anterior Ischemic Optic Neuropathy Following Cataract Surgery.

PURPOSE: To determine if there is an increased incidence rate of post-cataract surgery (pcs) anterior ischemic optic neuropathy (AION) compared to spontaneous AION (sAION). DESIGN: Retrospective, population-based cohort. METHODS: Patients diagnosed with AION from January 1, 1990, through December 31, 2016, while residing in Olmsted County, Minnesota. Patients with cataract surgery preceding AION were included in the pcsAION cohort defined in 2 ways: AION within 2 months and AION within 1 year of cataract surgery. The incidence rates of pcsAION and sAION were compared using Poisson regression models. RESULTS: During the study period, 102 residents developed AION. The median age was 65 years (range, 40-90 years), 44 (43.1%) were female. Twenty of 102 (19.6%) patients had previous cataract surgery, of which 2 and 9 developed AION within 2 months and 1 year of surgery, respectively. The annual incidence rate of pcsAION within 2 months of surgery (8.6 per 100,000) was not significantly greater than the annual incidence rate of sAION (6.9 per 100,000; P = .78). However, the annual incidence rate of pcsAION within 1 year of surgery (38.9 per 100,000) was significantly higher than the incidence rate of sAION (6.5 per 100,000; P < .001). CONCLUSION: The incidence of AION is increased in the first year after cataract surgery, but not in the early (i.e., 2 months) postoperative period.

Presentation and Progression of Papilledema in Cerebral Venous Sinus Thrombosis.

PURPOSE: To determine the natural history and visual outcomes of papilledema in cerebral venous sinus thrombosis (CVST). DESIGN: Retrospective observational case series. METHODS: This multicenter study included 7 tertiary care neuro-ophthalmology clinics. Sixty-five patients with CVST were identified who received serial eye examinations with documented papilledema from 2008-2016. Outcome measures included time from diagnosis to papilledema documentation, papilledema progression, time to papilledema resolution, treatment interventions and final visual outcomes. RESULTS: Papilledema was present on initial presentation in 54% of patients or detected later during the course of the disease in 46% of patients. The average time from CVST diagnosis to papilledema documentation was 29 days with a mean (SD) initial Frisén grade of 2.7 (1.3). In 21.5% of cases, papilledema progressed over an average of 55.6 (56.6) days. Time to papilledema resolution was approximately 6 months. Final visual acuity ranged from 20/20 to light perception, with 40% of patients having residual visual field defects on standard automated perimetry. Frisén grade ≥3 (odds ratio [OR] 10.21, P < .0053) and cases with worsening papilledema (3.5, P < .043) were associated with permanent visual field deficits. CONCLUSIONS: Our study indicates the importance of serial ophthalmic evaluation in all cases of CVST. Follow-up fundoscopy is critical given that a subset of cases can show delayed onset and/or worsening of papilledema with time. Specifically, we recommend an ophthalmic examination at the time of initial diagnosis, with repeat examination within a few weeks and further follow-up depending on the level of papilledema or vision changes.

Treatment Strategies for Neuroretinitis: Current Options and Emerging Therapies.

PURPOSE OF REVIEW: To explore and critically appraise the published data on the current and emerging treatment modalities for neuroretinitis. RECENT FINDINGS: The optimum treatment strategy for neuroretinitis due to Bartonella henselae in immunocompetent individuals is not clear and a matter of debate. The role of systemic corticosteroids in infectious neuroretinitis and the optimum immunosuppressive regimen for use in recurrent idiopathic neuroretinitis also remains ill defined. There is no class 1 evidence to support a specific treatment strategy for neuroretinitis. For uncomplicated B. henselae-associated neuroretinitis in immunocompetent patients, initiation of antibiotic and corticosteroid therapy remains controversial. In patients with severe vision loss and/or moderate to severe systemic symptoms, a 4- to 6-week regimen of doxycycline or azithromycin with rifampin may provide some benefit. The routine use of systemic corticosteroids in infectious neuroretinitis is not recommended. Targeted antimicrobial agents should be instituted in cases of neuroretinitis due to specific infectious etiologies (e.g., syphilis, Lyme disease, tuberculosis). Azathioprine may be beneficial in cases of recurrent idiopathic neuroretinitis. There is a need for collaborative, multicenter prospective studies to provide definitive guidelines regarding the use of antibiotics and corticosteroids and to evaluate future therapies in infectious and recurrent idiopathic neuroretinitis.

Urinary ß2-microglobulin and disease activity in patients with tubulointerstitial nephritis and uveitis syndrome.

BACKGROUND: Urinary ß2-microglobulin (Uß2M) is elevated in tubulointerstitial nephritis and uveitis (TINU) syndrome and has emerged as an important diagnostic tool. This study aims to determine whether Uß2M correlates with uveitis activity in TINU. METHODS: Retrospective observational case series of nine patients with TINU and ≥ 30 days follow-up. Presenting symptoms, visual acuity, uveitis characteristics, follow-up, Uß2M, serum creatinine (SCr), urinalysis, and renal biopsy results were collected. RESULTS: A correlation between Uß2M and anterior chamber (AC) cell (r = 0.69, 95% CI 0.46-0.84), flare (r = 0.65, 95% CI 0.39-0.81), trended toward a stronger correlation than SCr and AC cell (r = 0.59, 95% CI 0.29-0.79), flare (r = 0.52, 95% CI 0.19-0.75). Uß2M decreased over 1-2 years while SCr returned to normal within a few months. CONCLUSIONS: Uß2M correlate with uveitis activity and trend down over the course of TINU. Uß2M may serve as a useful tool in determining where patients are in their systemic disease course.

Peripherally administered calcitonin gene-related peptide induces spontaneous pain in mice: implications for migraine.

Migraine is the third most common disease in the world (behind dental caries and tension-type headache) with an estimated global prevalence of 15%, yet its etiology remains poorly understood. Recent clinical trials have heralded the potential of therapeutic antibodies that block the actions of the neuropeptide calcitonin gene-related peptide (CGRP) or its receptor to prevent migraine. Calcitonin gene-related peptide is believed to contribute to trigeminal nerve hypersensitivity and photosensitivity in migraine, but a direct role in pain associated with migraine has not been established. In this study, we report that peripherally administered CGRP can act in a light-independent manner to produce spontaneous pain in mice that is manifested as a facial grimace. As an objective validation of the orbital tightening action unit of the grimace response, we developed a squint assay using a video-based measurement of the eyelid fissure, which confirmed a significant squint response after CGRP injection, both in complete darkness and very bright light. These indicators of discomfort were completely blocked by preadministration of a monoclonal anti-CGRP-blocking antibody. However, the nonsteroidal anti-inflammatory drug meloxicam failed to block the effect of CGRP. Interestingly, an apparent sex-specific response to treatment was observed with the antimigraine drug sumatriptan partially blocking the CGRP response in male, but not female mice. These results demonstrate that CGRP can induce spontaneous pain, even in the absence of light, and that the squint response provides an objective biomarker for CGRP-induced pain that is translatable to humans.