Central Retinal Artery Occlusion With Subsequent Central Retinal Vein Occlusion in Biopsy-Proven Giant Cell Arteritis.

Central retinal artery occlusion with subsequent central retinal vein occlusion in the same eye is a rare entity. We present a 72-year-old man with biopsy-proven giant cell arteritis who developed bilateral arteritic anterior ischemic optic neuropathy and a left central retinal artery occlusion. Subsequently, he developed a left central retinal vein occlusion within 2 weeks of his initial vision loss. His vision did not improve with corticosteroids.

Focal damage to macaque photoreceptors produces persistent visual loss.

Insertion of light-gated channels into inner retina neurons restores neural light responses, light evoked potentials, visual optomotor responses and visually-guided maze behavior in mice blinded by retinal degeneration. This method of vision restoration bypasses damaged outer retina, providing stimulation directly to retinal ganglion cells in inner retina. The approach is similar to that of electronic visual protheses, but may offer some advantages, such as avoidance of complex surgery and direct targeting of many thousands of neurons. However, the promise of this technique for restoring human vision remains uncertain because rodent animal models, in which it has been largely developed, are not ideal for evaluating visual perception. On the other hand, psychophysical vision studies in macaque can be used to evaluate different approaches to vision restoration in humans. Furthermore, it has not been possible to test vision restoration in macaques, the optimal model for human-like vision, because there has been no macaque model of outer retina degeneration. In this study, we describe development of a macaque model of photoreceptor degeneration that can in future studies be used to test restoration of perception by visual prostheses. Our results show that perceptual deficits caused by focal light damage are restricted to locations at which photoreceptors are damaged, that optical coherence tomography (OCT) can be used to track such lesions, and that adaptive optics retinal imaging, which we recently used for in vivo recording of ganglion cell function, can be used in future studies to examine these lesions.

Inner limiting Membrane Peel Extends In vivo Calcium Imaging of Retinal Ganglion Cell Activity Beyond the Fovea in Non-Human Primate.

High resolution retinal imaging paired with intravitreal injection of a viral vector coding for the calcium indicator GCaMP has enabled visualization of activity dependent calcium changes in retinal ganglion cells (RGCs) at single cell resolution in the living eye. The inner limiting membrane (ILM) is a barrier for viral vectors, restricting transduction to a ring of RGCs serving the fovea in both humans and non-human primates (NHP). We evaluate peeling the ILM prior to intravitreal injection as a strategy to expand calcium imaging beyond the fovea in the NHP eye in vivo. Five Macaca fascicularis eyes (age 3-10y; n=3 individuals; 2M, 1F) underwent vitrectomy and 5 to 6-disc diameter ILM peel centered on the fovea prior to intravitreal delivery of 7m8:SNCG:GCaMP8s. Calcium responses from RGCs were recorded using a fluorescence adaptive optics scanning laser ophthalmoscope. In all eyes GCaMP was expressed throughout the peeled area, representing a mean 8-fold enlargement in area of expression relative to a control eye. Calcium recordings were obtained up to 11 degrees from the foveal center. RGC responses were comparable to the fellow control eye and showed no significant decrease over the 6 months post ILM peel, suggesting that RGC function was not compromised by the surgical procedure. In addition, we demonstrate that activity can be recorded directly from the retinal nerve fiber layer. This approach will be valuable for a range of applications in visual neuroscience including pre-clinical evaluation of retinal function, detecting vision loss, and assessing the impact of therapeutic interventions.

Infectious endophthalmitis in adult eyes receiving Boston type I keratoprosthesis.

PURPOSE: To report the clinical characteristics of infectious endophthalmitis after Boston type I keratoprosthesis (K-Pro) implantation. DESIGN: Retrospective study. PARTICIPANTS: One hundred forty-one adult eyes receiving a K-Pro at a single institution from May 2004 through July 2008. METHODS: A retrospective chart review was performed of all adult eyes receiving a K-Pro at the University of Rochester from May 2004 through July 2008. Those patients identified as having been treated for exogenous bacterial endophthalmitis were reviewed for demographic data, indication for K-Pro, bandage contact lens use, prophylactic antibiotic use, timing and clinical presentation of endophthalmitis, gram stain and culture results of intraocular fluid, timing and presentation of any subsequent episodes of endophthalmitis (recurrent endophthalmitis), and preoperative and postoperative visual acuity through August 2010. MAIN OUTCOME MEASURES: Incidence of endophthalmitis, time to occurrence, recurrence rates, visual outcomes, and risk factors associated with K-Pro endophthalmitis. RESULTS: Ten (7.1%) of 141 eyes of 130 adult patients were diagnosed and treated for bacterial endophthalmitis. Average time to endophthalmitis developing after K-Pro was 9.8 months (standard deviation [SD], 6.2 months; range, 2-25 months). Coagulase-negative staphylococci were identified in 7 eyes. In 7 of the 10 eyes, recurrent endophthalmitis developed that occurred at a mean of 4 months (SD, 3.9 months; range, 1-13 months) after resolution of the initial episode. At each episode of endophthalmitis, no eye was receiving vancomycin ophthalmic drops and most eyes were receiving only fluoroquinolone ophthalmic drops for prophylaxis. CONCLUSIONS: Infectious endophthalmitis after K-Pro implantation has a higher incidence, delayed onset, and high risk for recurrence compared with postoperative endophthalmitis associated with more common intraocular procedures such as cataract surgery. The concurrent use of topical vancomycin is recommended because it seems to be important in reducing the incidence and recurrence of endophthalmitis and because fluoroquinolone ophthalmic drops do not seem to be sufficient prophylaxis in these eyes.

Steroid Allergy in a Patient With Behçet's Disease.

Immediate hypersensitivity reactions to systemic steroids are reported rarely in the literature. The authors present a case of Behçet's disease-associated panuveitis in a patient with skin test confirmed immunoglobulin E-mediated allergy to methylprednisolone and reported allergic reaction to prednisone. The patient tolerated prednisolone eyedrops for his anterior segment disease, as well as oral prednisolone for systemic therapy. This case demonstrates a challenge to conventional treatment, as it involves a hypersensitivity that is rarely reported. It also highlights class differences in corticosteroids with regard to immune reactivity. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:447-449.].

Quantitative Comparison of Fundus Images by 2 Ultra-Widefield Fundus Cameras.

PURPOSE: To compare the relative number of retinal pixels and retinal area imaged using the Optos P200DTx (Optos PLC) and Zeiss Clarus 500 (Carl Zeiss Meditec AG) ultra-widefield (UWF) fundus cameras. DESIGN: Single-center retrospective cross-sectional analysis. PARTICIPANTS: Seventy-eight eyes of 46 patients. METHODS: Eyes were imaged with Optos P200DTx, single-capture, and Zeiss Clarus 500, 2 capture montages when possible, UWF fundus cameras. Relative number of pixels encompassing all foveal-centered retinal quadrants were measured. Retinal area was measured with Zeiss Clarus 500 images that were registered to the Optos P200DTx images. Patients and technicians were asked for preferences between the machines. Imaging session times were recorded. MAIN OUTCOME MEASURES: Relative number of retinal pixels and retina area captured by each fundus camera. RESULTS: Optos P200DTx consistently captured more relative pixels compared with Zeiss Clarus 500: 510.4 versus 355.6 (P < 0.001) in total with a similarly statistically significant trend in all 4 quadrants (P < 0.001 for each). For area calculation, 70 of the 78 images achieved successful registration. Optos captured a larger total retinal area: 765.6 versus 566.5 mm2 (P < 0.001) with a similarly statistically significant trend in all 4 quadrants. In the subset of 52 of 70 registered and montaged Zeiss Clarus 500 images, similar results were found. For peripheral pathologic features, Optos P200DTx captured unique findings in 28 images, and Zeiss Clarus 500 captured unique findings 1 image (P < 0.001). Among the 48 imaging sessions in which technicians preferred Optos P200DTx for 28 sessions (58%) and Zeiss Clarus 500 for 20 (42%; P = 0.15). Among patients who responded with a preference, 24 preferred Optos P200DTx and 20 preferred Zeiss Clarus 500 (P = 0.52). Average imaging session time was 4.6 minutes (standard deviation, 3.0 minutes) for Optos P200DTx and 5.2 minutes (standard deviation, 3.0 minutes) for Zeiss Clarus 500 (P = 0.17). CONCLUSIONS: In the current study, the Optos P200DTx captured statistically significantly more retinal area in all 4 quadrants compared with the Zeiss Clarus 500. No statistically significant difference was found in patient or technician preference or image acquisition time between devices.

Spontaneous Resolution of a Choroidal Mass: A Case Series.

Choroidal masses can be of varying etiologies including tumors of benign, primary, and metastatic nature. Herein, we report on 3 cases of well-documented solitary choroidal masses associated with exudative retinal detachments of unclear etiology (despite extensive workup) that resolved spontaneously.

Imaging Transplanted Photoreceptors in Living Nonhuman Primates with Single-Cell Resolution.

Stem cell-based transplantation therapies offer hope for currently untreatable retinal degenerations; however, preclinical progress has been largely confined to rodent models. Here, we describe an experimental platform for accelerating photoreceptor replacement therapy in the nonhuman primate, which has a visual system much more similar to the human. We deployed fluorescence adaptive optics scanning light ophthalmoscopy (FAOSLO) to noninvasively track transplanted photoreceptor precursors over time at cellular resolution in the living macaque. Fluorescently labeled photoreceptors generated from a CRX+/tdTomato human embryonic stem cell (hESC) reporter line were delivered subretinally to macaques with normal retinas and following selective ablation of host photoreceptors using an ultrafast laser. The fluorescent reporter together with FAOSLO allowed transplanted photoreceptor precursor survival, migration, and neurite formation to be monitored over time in vivo. Histological examination suggested migration of photoreceptor precursors to the outer plexiform layer and potential synapse formation in ablated areas in the macaque eye.

Retinal arteriolar spasm during transient monocular visual loss in eosinophilic vasculitis.

A patient with eosinophilic vasculitis and acquired immunodeficiency syndrome (AIDS) developed episodic transient monocular visual loss. During or immediately after two visual loss episodes, we demonstrated narrowed retinal arterioles, delayed arterial filling time, and segmented retinal venous flow in the affected eye on fundus photography and fluorescein angiography (FA). Such findings have only rarely been reported in patients with transient monocular visual loss in other conditions, probably because the episodes have ended before fundus photography and FA could be performed. This is the first report to capture retinal vascular changes associated with transient monocular visual loss in a patient with eosinophilic vasculitis.

Cellular-scale evaluation of induced photoreceptor degeneration in the living primate eye.

Progress is needed in developing animal models of photoreceptor degeneration and evaluating such models with longitudinal, noninvasive techniques. We employ confocal scanning laser ophthalmoscopy, optical coherence tomography (OCT) and high-resolution retinal imaging to noninvasively observe the retina of non-human primates with induced photoreceptor degeneration. Photoreceptors were imaged at the single-cell scale in three modalities of adaptive optics scanning light ophthalmoscopy: traditional confocal reflectance, indicative of waveguiding; a non-confocal offset aperture technique visualizing scattered light; and two-photon excited fluorescence, the time-varying signal of which, at 730 nm excitation, is representative of visual cycle function. Assessment of photoreceptor structure and function using these imaging modalities revealed a reduction in retinoid production in cone photoreceptor outer segments while inner segments appeared to remain present. Histology of one retina confirmed loss of outer segments and the presence of intact inner segments. This unique combination of imaging modalities can provide essential, clinically-relevant information on both the structural integrity and function of photoreceptors to not only validate models of photoreceptor degeneration but potentially evaluate the efficacy of future cell and gene-based therapies for vision restoration.

In Vivo Adaptive Optics Ophthalmoscopy Correlated with Histopathologic Results in Cancer-Associated Retinopathy.

PURPOSE: To demonstrate the validity of adaptive optics scanning laser ophthalmoscopy (AOSLO) imaging of the retina in human disease based on clinicopathologic correlation in a patient with cancer-associated retinopathy (CAR). DESIGN: Case report. PARTICIPANT: Sixty-four-year-old man with CAR. METHODS: Fundus photography, electroretinography, visual field testing, fundus autofluorescent imaging, spectral-domain OCT scans, AOSLO, and histopathologic analysis were performed. MAIN OUTCOME MEASURE: Comparison of AOSLO with histopathologic results. RESULTS: Changes in photoreceptor morphologic features were correlated highly between AOSLO and histopathologic results. CONCLUSIONS: We present a unique case where a patient with a rare and fatal disease, CAR, underwent AOSLO imaging during the course of the disease, and then shortly thereafter, postmortem histopathologic analysis of the eyes was carried out. This is the first report of use of AOSLO to elucidate further the retinal changes that occur in CAR and the first study to demonstrate correlation of AOSLO with histopathologic results in any human disease.

A 9 year-old girl with herpes simplex virus type 2 acute retinal necrosis treated with intravitreal foscarnet.

A 9-year-old girl presented with a 2-week history of redness in the left eye. Examination revealed vitritis, retinal whitening, vasculitis, and optic nerve head edema. Polymerase chain reaction testing of the aqueous fluid revealed herpes simplex virus type 2. The retinitis was controlled with intravenous acyclovir and intravitreal foscarnet. The clinical course was complicated by retinal neovascularization and vitreous hemorrhage, which was treated by pars plana vitrectomy and endolaser. While there are few case reports of herpes simplex virus type 2 retinitis in children, this one is unique for the following reasons: it is the first reported case of herpes simplex virus type 2 retinitis in a child less than 10 years old without a previous history of neonatal infection or central nervous system involvement; no other children have been reported to have been treated with intravitreal foscarnet; and retinal neovascularization complicated the recovery.

CRYSTALLINE RETINOPATHY FROM HYPEROXALURIA: LONG-TERM FOLLOW-UP.

PURPOSE: To report long-term follow-up in a patient with retinal oxalosis from primary hyperoxaluria. METHODS: Retrospective chart review was performed for this patient. PATIENTS: A 6-year-old girl that presented to our clinic before and after combined kidney/liver transplant. RESULTS: Optical coherence tomography and fundus findings consistent with oxalate crystal deposition. CONCLUSION: Progressive macular changes, including atrophy and fibrosis can occur in crystalline retinopathy, secondary to hyperoxaluria, after combined hepatorenal transplant.

An ultrastructural study of the pathology of the retinal pigment epithelium, Bruch's membrane, and the choriocapillaris in the aged Fischer 344 rat.

PURPOSE: The neural retinal degeneration in the aging Fischer 344 (F344) rat has been previously characterized. Here we describe the ultrastructural changes that occur in the retinal pigment epithelium (RPE), Bruch's membrane, and choriocapillaris in the periphery of the aged Fischer 344 rat. METHODS: F344 eyes from 24-month-old animals (n = 4 animals, 8 eyes) were fixed and embedded for ultrastructural study. Serial mid-sagittal sections were taken from the superior peripheral retinas within 300 microm of the ora serrata. Pathology within the RPE, Bruch's membrane, and choriocapillaris was described. RESULTS: Progressive changes were seen in the RPE/Bruch's/choriocapillaris complex, increasing anteriorly as the ora serrata was approached. Early pathology of the RPE included increased number of basal infoldings, increased number of phagolysosomes and lipofuscin deposits, attenuation, inclusion of vasculature, vesicle formation, and whirling extensions of the basement membrane into the cytoplasm. Bruch's membrane showed spots of considerable thinning, but most prominent was the nodular thickening. The choriocapillaris was found to have severe endothelial degeneration and transformation to fibrous tissue in the most severely affected regions. Lipofuscin was also found in areas of degenerated choriocapillaris. CONCLUSIONS: Prior work focused on the neural retina, documented photoreceptor cell loss, and showed that Müller cell changes preceded that loss in the periphery of the F344 rat. It is now evident that the pathology in the RPE/Bruch's membrane/choriocapillaris complex may also be a critical component of the overall degenerative process. A possible mechanism for the extensive peripheral retinal degeneration in the F344 is presented.

Immunologic factors may play a role in herpes simplex virus 1 reactivation in the brain and retina after influenza vaccination.

Herpes simplex virus 1 (HSV-1) is a nearly ubiquitous human pathogen, remaining dormant in its human host the majority of the time. The interaction between HSV-1 and the immune system represents a complicated balance of power that allows the virus to persist in the host for a lifetime. However, disruptions in the immune system can activate the virus with the potential to cause devastating infections in the central nervous system (CNS). We present a patient who suffered three consecutive yearly HSV-1 CNS episodes (encephalitis, seizure, and retinitis), each within days of his influenza vaccination. We highlight subtle immunologic defects in this patient that may have allowed unchecked viral replication and resultant disease manifestations, as well as the potential role of influenza vaccine in tipping this balance in favor of HSV-1.

Use of best and final visual acuity outcomes in ophthalmological research.

OBJECTIVE: To evaluate how often visual acuity outcomes are reported in the ophthalmological literature as best or final outcomes, despite potential bias with this type of analysis, as compared with interval outcomes, when a specific condition may continue to cause gain or loss of visual acuity beyond the time that the best or final outcome is determined. METHODS: Each article published in the 3 most frequently cited comprehensive clinical ophthalmological journals in the United States from January through December 2000 was reviewed. Clinical studies were identified in which visual acuity was used as an outcome measure. Visual acuity outcomes were examined throughout the articles and classified as follows: best visual acuity, defined as an outcome at any time during follow-up; final visual acuity, defined as an outcome at last follow-up; and interval visual acuity, defined as an outcome at specified follow-up times. A few factors that might be associated with the different types of outcome were evaluated. Reproducibility of the categorization between 2 ophthalmologists evaluating the articles was determined by using the kappa statistic. RESULTS: A total of 527 clinical studies met the criteria. Among these, authors of 195 reported visual acuity as an outcome measure. Authors of 1 article (0.5%) reported only best visual acuity, authors of 6 (3%) reported both best and final visual acuity, authors of 113 (58%) reported only final visual acuity, and authors of 73 (37%) reported interval visual acuity outcomes. Reproducibility of these categorizations between 2 ophthalmologists was considered excellent, as compared with chance alone (kappa = 0.84). Authors of only 2 of the 120 articles that used either best or final visual acuity outcomes discussed the limitations or potential bias of reporting outcomes in this way. Randomized trials and other prospective study designs more often were associated with interval outcomes than were nonrandomized and retrospective studies. CONCLUSIONS: Despite potential bias with use of best or final visual acuity outcomes, these end points alone were used in most studies published during 2000 in the 3 most commonly cited journals. Authors of clinical studies should consider avoiding use of best or final visual acuity outcomes whenever possible to minimize possible data misinterpretation. If best or final outcomes are used, authors should consider discussing the limitations of these methods and their potential effect on the interpretation of results.

Late-onset bacteria endophthalmitis following glaucoma drainage implantation.

A clinicopathologic report of late-onset bacterial endophthalmitis 4 years after implantation of a Baerveldt drainage implant is described. An 80-year-old woman with glaucoma presented 8 years after tube shunt implantation with clinical endophthalmitis. During surgical removal of the implant, a small conjunctival buttonhole caused by the suture securing the plate to the sclera was noted to be the only entry site. Vitreous and anterior chamber taps were performed with intravitreal antibiotics. Cultures revealed Streptococcus pneumoniae infection. The pathologic analysis showed epithelialization of the conjunctival button-hole and diffuse ocular inflammation, mucopurulent material, and fibrovascular membranes. Due to severe pain, the eye was enudeated after 1 week.

Late-onset bacterial endophthalmitis following glaucoma drainage implantation.

Abstract. A clinicopathologic report of late-onset bacterial endophthalmitis 4 years after implantation of a Baerveldt drainage implant is described. An 80-yearold woman with glaucoma presented 8 years after tube shunt implantation with clinical endophthalmitis. During surgical removal of the implant, a small conjunctival buttonhole caused by the suture securing the plate to the sclera was noted to be the only entry site. Vitreous and anterior chamber taps were performed with intravitreal antibiotics. Cultures revealed Streptococcus pneumoniae infection. The pathologic analysis showed epithelialization of the conjunctival buttonhole and diffuse ocular inflammation, mucopurulent material, and fibrovascular membranes. Due to severe pain, the eye was enucleated after 1 week. [Ophthalmic Surg Lasers Imaging 2003;34:128-130.].

Migration of intravitreal dexamethasone implant to anterior chamber.

PURPOSE: To describe two cases of migration of intravitreally injected dexamethasone implant into the anterior chamber. METHODS: Charts were reviewed of two patients who received sustained-release dexamethasone implant intravitreally for chronic intractable cystoid macular edema. RESULTS: Both patients had pseudophakic cystoid macular edema and a complicated clinical course before receiving the implant. Treatments before intravitreal injection of implant included topical nonsteroidal anti-inflammatory drugs, sub-Tenon triamcinolone injections, vitrectomy, and, in one case, intravitreal bevacizumab. Both patients responded well to triamcinolone injections but required repeated injections. This led to the decision to inject the implant. Within 2 weeks of injection, the implant was noted in the anterior chamber causing pain and decreased vision from corneal edema. Both patients underwent successful removal of the implant. CONCLUSION: Sustained-release intravitreal injectable implants can migrate freely in vitrectomized pseudophakic or aphakic eyes. Selection of a scleral-fixated steroid implant might be safer in such cases.

Esophageal metastasis to the iris effectively palliated using stereotactic body radiation therapy and adjuvant intravitreal chemotherapy: case report and literature review.

We report a case of isolated iris metastasis from esophageal adenocarcinoma that was successfully managed with local application of stereotactic body radiation therapy (SBRT) and adjunctive intravitreal therapy. A 53-year-old man with locally advanced esophageal adenocarcinoma achieved a complete clinical and radiographic response after surgery and chemotherapy. Four months later, he developed headache and decreased vision and was diagnosed with metastasis to the iris by slit-lamp examination. The decrease in vision was secondary to cystoid macular edema. The metastatic tumor and the patient's symptoms resolved after treatment with SBRT and intravitreal injections of bevacizumab and triamcinolone. We conclude that SBRT combined with intravitreal chemotherapy is an effective and well-tolerated palliative treatment for metastasis of esophageal adenocarcinoma to the iris.