Occlusive Vasculitis Following Intravitreal Rituximab Injection for Primary Vitreoretinal Lymphoma.

PURPOSE: We report three cases of occlusive vasculitis following intravitreal rituximab therapy for biopsy-proven primary vitreoretinal lymphoma (PVRL), one of which was following an injection of the biosimilar Riabni (rituximab-arrx, AmGen) and two of which were following an injection of Rituxan (rituximab, Genentech). METHODS: Case series. RESULTS: Three cases of occlusive vasculitis confirmed with fluorescein angiography are reported 5 days, 8 days, and 3.5 weeks following intravitreal injection of rituximab. The initial vision was poor (20/500, 20/150, and light perception), but vision recovered to baseline in two cases, and remained poor in the case of combined artery and vein occlusion. CONCLUSION: Occlusive vasculitis is a rarely reported but potential complication of intravitreal rituximab therapy in patients who have been previously treated with the agent and may have delayed onset. A low threshold for fluorescein angiography as a diagnostic test for post-injection vision loss and prompt treatment with topical and/or oral steroids should be considered.

Combined Face and Whole Eye Transplantation: Cadaveric Rehearsals and Feasibility Assessment.

Background: In properly selected patients, combined face and whole eye transplantation (FWET) may offer a more optimal aesthetic and potentially functional outcome while avoiding the complications and stigma of enucleation and prosthetics. This study presents the most comprehensive cadaveric assessment for FWET to date, including rehearsal allograft procurement on a brain-dead donor. Methods: Over a 2-year period, 15 rehearsal dissections were performed on 21 cadavers and one brain-dead donor. After identification of a potential recipient, rehearsals assessed clinical feasibility and enabled operative planning, technical practice, refinement of personalized equipment, and improved communication among team members. Operative techniques are described. Results: Facial allograft procurement closely followed previously described face transplant techniques. Ophthalmic to superficial temporal (O-ST) vessel anastomosis for globe survival was assessed. Craniectomy allowed for maximal optic nerve and ophthalmic vessel pedicle length. Appropriate pedicle length and vessel caliber for O-ST anastomosis was seen. Research procurement demonstrated collateral blood flow to the orbit and surrounding structures from the external carotid system as well as confirmed the feasibility of timely O-ST anastomosis. Personalized cutting guides enabled highly accurate bony inset. Conclusions: This study formalizes an approach to FWET, which is feasible for clinical translation in judiciously selected patients. O-ST anastomosis seems to minimize retinal ischemia time and allow perfusion of the combined allograft on a single external carotid pedicle. Although restoration of vision likely remains out of reach, globe survival is possible.

The impact of the COVID-19 lockdown on retinopathy of prematurity screening and management in the United States: a multicenter study.

PURPOSE: To study the effect of the pandemic-related lockdown (physical distance measures and movement restrictions) on the characteristics and management of retinopathy of prematurity (ROP). METHODS: In this controlled, multicenter cohort study, the medical records of patients born prematurely and screened for ROP in the neonatal intensive care unit during four time periods were reviewed retrospectively: (1) November 1, 2018, to March 15, 2019; (2) March 16, 2019, to August 2, 2019 (lockdown control period); (3) November 1, 2019, to March 15, 2020; and (4) March 16, 2020-August 2, 2020. RESULTS: A total of 1,645 patients met inclusion criteria. Among the 1,633 patients with complete data, mean gestational age (GA) at birth was 28.2, 28.4, 28.0, and 28.3 weeks across time periods 1 to 4, respectively (P = 0.16). The mean birth weight of all patients was 1079.1 ± 378.60 g, with no significant variation across time periods (P = 0.08). There were fewer patients screened during the lockdown period (n = 411) compared with the period immediately before (n = 491) and the same period in the prior year (n = 533). Significantly more patients were screened using indirect ophthalmoscopy, compared to digital imaging (telemedicine), during the lockdown (P < 0.01). There were 11.7%, 7.7%, 9.0%, and 8.8% of patients requiring treatment in each time period, respectively (P = 0.42), with a median postmenstrual age at initial treatment of 37.2, 36.45, 37.1, and 36.3 weeks, respectively (P = 0.32). CONCLUSIONS: We recorded a decrease in the number of infants meeting criteria for ROP screening during the lockdown. The GA at birth and birth weight did not differ. Significantly more infants were screened with indirect ophthalmoscopy, compared to digital imaging, during the lockdown.

Follow-up Rates After Teleretinal Screening for Diabetic Retinopathy: Assessing Patient Barriers to Care.

Purpose: To study patient follow-up after they engage in a teleretinal screening program and to understand potential barriers to care. Methods: This was a retrospective analysis and a prospective study of telephone-based patient interviews of outpatients screened for diabetic retinopathy (DR) through a teleretinal referral system. Results: Of 2761 patients screened through a teleretinal referral program, 123 (4.5%) had moderate nonproliferative DR (NPDR), 83 (3.0%) had severe NPDR, and 31 (1.1%) had proliferative DR. Of the 114 patients with severe NPDR or worse, 67 (58.8%) saw an ophthalmologist within 3 months of referral. Eighty percent of interviewed patients reported they were not aware of the need for follow-up eye appointments. Conclusions: Of patients with severe retinopathy or worse, 58.8% presented for in-person evaluation and treatment within 3 months of screening. Although this result was negatively affected by factors related to the COVID-19 pandemic, key elements of patient education and improved referral strategies to facilitate in-person treatment are essential to improving follow-up after patients engage in telescreening.

PARACENTRAL ACUTE MIDDLE MACULOPATHY ASSOCIATED WITH HYPERCOAGULABILITY IN PREGNANCY.

PURPOSE: To report a case of paracentral acute middle maculopathy in an otherwise healthy young, multiparous woman in her second trimester of pregnancy. METHODS: A case report. RESULTS: A 38-year-old woman in her twentieth week of pregnancy presented with a four-day history of an acute paracentral scotoma in her left eye. Fundoscopic examination of the left eye was significant for a white-gray lesion inferonasal to the fovea which corresponded with spectral-domain optical coherence tomography hyperreflectivity at the outer plexiform layer-inner nuclear layer junction and optical coherence tomography angiography nonperfusion. A diagnosis of paracentral acute middle maculopathy was made. The patient was sent for a hypercoagulability workup that revealed elevated Factor VIII activity, which has been associated with increased risk of complications during pregnancy. CONCLUSION: Paracentral acute middle maculopathy in pregnancy may be secondary to an underlying hypercoagulable condition. We recommend systemic evaluation and referral to a high-risk pregnancy specialist if paracentral acute middle maculopathy is diagnosed during pregnancy. In addition, optical coherence tomography angiography in paracentral acute middle maculopathy may demonstrate reperfusion of the affected vessels.

Intraocular Metastasis of Large T-cell Lymphoma Transformed from Mycosis Fungoides.

PURPOSE: To describe a rare case of intraocular lymphoma that metastasized from cutaneous mycosis fungoides and transformed to large cell T cell lymphoma resulting in vitreoretinal pathology. METHODS: Retrospective case report. RESULTS: A 57-year-old male presented with 3 months of blurred vision in the right eye. He reported only a medical history of psoriasis. Examination revealed keratic precipitates and dense vitritis in the right eye. He was taken for a diagnostic vitrectomy. Histopathology showed that atypical lymphoid cells and flow cytometry were consistent with transformed large cell T-cell lymphoma. During follow-up, pre- and inner retinal lesions were noted throughout the posterior pole. Histopathology of the psoriatic lesions was consistent with mycosis fungoides. He was initiated on systemic and intravitreal methotrexate with improvement in vision. CONCLUSIONS: Ocular involvement in metastatic transformed T-cell lymphoma is extremely rare but can be present with vitritis and retinal deposits. Our patient responded well to intravitreal methotrexate therapy.

COMBINED HAMARTOMA OF THE RETINA AND RETINAL PIGMENT EPITHELIUM AT PEDIATRIC AGE: Surgical Versus Conservative Approach.

PURPOSE: To report outcomes of pediatric patients with combined hamartoma of the retina and the retina pigment epithelium followed up conservatively or after pars plana vitrectomy. METHODS: This retrospective multicenter study included 62 eyes of 59 pediatric patients with combined hamartoma of the retina and the retina pigment epithelium from 13 different international centers with an average age of 7.7 ± 4.7 (0.3-17) years at the time of the diagnosis and having undergone pars plana vitrectomy or followed conservatively. At baseline and each visit, visual acuity values, optical coherence tomography for features and central foveal thickness, and tumor location were noted. Lesions were called as Zone 1, if it involves the macular and peripapillary areas, and the others were called as Zone 2 lesions. RESULTS: Twenty-one eyes of 20 patients in the intervention group and 41 eyes of 39 patients in the conservative group were followed for a mean of 36.2 ± 40.4 (6-182) months. Best-corrected visual acuity improved in 11 (68.8%) of 16 eyes in the intervention group and 4 (12.9%) of 31 eyes in the conservative group ( P < 0.001). The mean central foveal thickness decreased from 602.0 ± 164.9 µ m to 451.2 ± 184.3 µ m in the intervention group, while it increased from 709.5 ± 344.2 µ m to 791.0 ± 452.1 µ m in Zone 1 eyes of the conservative group. Posterior location of tumor, irregular configuration of the foveal contour and ellipsoid Zone defect in optical coherence tomography, subretinal exudate and prominent vascular tortuosity were associated with poor visual acuity. CONCLUSION: Vitreoretinal surgery is safe and effective in improving vision and reducing retinal distortion in Zone 1 combined hamartoma of the retina and the retina pigment epithelium in children.

Endophthalmitis, Visual Outcomes, and Management Strategies in Eyes with Intraocular Foreign Bodies.

Purpose: Ocular trauma with intraocular foreign body (IOFB) can have devastating visual consequences. Management and antimicrobial strategies remain variable due to the infrequency and heterogeneity of presentation. Our goal was to identify risk factors for endophthalmitis and poor visual outcomes in cases of IOFB and investigate management strategies. Patients and Methods: A retrospective chart review was conducted in 88 eyes of 88 patients suffering traumatic injury with IOFB at the University of Michigan between January 2000 and December 2019. Medical records were reviewed to characterize the injuries and IOFBs as well as how clinical presentation and treatment modalities were associated with outcomes. Results: Delayed presentation (P=0.016) and organic IOFB (P=0.044) were associated with development of endophthalmitis. Retinal detachment (P=0.012), wound length greater than 5 mm (P=0.041), and poor presenting visual acuity (P=0.003) correlated with poor final visual outcome. Antibiotic prophylaxis was given to all patients, though agents and routes of delivery varied. Endophthalmitis developed in 4.9% of the eyes after initial management, with primary and secondary removal of posterior segment IOFBs associated with similar rates of endophthalmitis (P=1.000). Conclusion: Poor presenting visual acuity and severity of injury, as measured by large wound and retinal detachment, correlate with poor visual outcome. Prompt globe closure and antimicrobial prophylaxis are critical for infection prevention. In cases where IOFB removal and globe closure cannot be performed concurrently, primary globe closure with aggressive antibiotic prophylaxis offers a reasonable alternative to prevent endophthalmitis.

Improved Prognostic Precision in Uveal Melanoma through a Combined Score of Clinical Stage and Molecular Prognostication.

Introduction: Prognosis of uveal melanoma (UM) is assessed using clinical staging or molecular testing. Two modalities often used for prognostication are the American Joint Committee on Cancer (AJCC) staging and a tumor gene expression profile (GEP), the outcomes of which are often discordant. This article discusses a total risk score created to combine the discordant information from both sources. Methods: A retrospective case series was conducted of all patients presenting with UM over 6 years to 2 referral centers. Each tumor was classified using the AJCC and the GEP. A total risk score was calculated for each patient using results from both AJCC and GEP. Kaplan-Meier analysis of metastasis-free survival was used to compare groups. Results: A total of 294 patients were included in the study. Kaplan-Meier estimates showed significant curve separation between individual AJCC and GEP risk groups. The combined total risk score provided an accurate estimate of prognosis that incorporated results from both AJCC and GEP. Conclusions: Clinical staging and molecular prognostication of UM can be discordant. There is important information provided by each system that is not provided by the other. The total risk score provides a simple method to combine information from both AJCC stage and the GEP class in order to provide patients and care teams with a more complete understanding of metastatic risk.

Risk Factors for Endophthalmitis Following Open Globe Injuries: A 17-Year Analysis.

BACKGROUND/AIMS: To determine the rate of endophthalmitis and assess risk factors for development of endophthalmitis following open globe injury (OGI). METHODS: A retrospective chart review of all patients treated for OGI at the University of Michigan from January 2000 to July 2017 was conducted. Exclusion criteria included intravitreal injection or intraocular surgery in the 30 days prior to injury or less than 30 days of follow-up. A total of 586 out of 993 open globe injuries were included in the study. The main outcome measure was the rate of endophthalmitis. RESULTS: In this study, 25/586 eyes (4.3%) had endophthalmitis. Of these, 12/25 eyes (48.0%) presented with endophthalmitis and 13/25 eyes (52.0%) developed endophthalmitis after globe closure. Multivariate analysis identified time to globe repair (OR 4.5, CI 1.9-10.7, p = 0.0008), zone I injury (OR 3.6, CI 1.1-11.0, p = 0.0282), and need for additional surgery (OR 5.5, CI 1.5-19.7, p = 0.0092) as factors associated with increased risk of developing endophthalmitis. Subconjunctival antibiotic injection at the time of globe closure (OR 0.3, CI 0.1-0.7, p = 0.0036) was associated with decreased risk of developing endophthalmitis. CONCLUSION: Prompt globe closure and subconjunctival antibiotics may reduce the risk of endophthalmitis in OGI. Furthermore, our practice of a one-time dose of systemic prophylactic antibiotics, and intravitreal antibiotics if intraocular foreign body (IOFB) removal is delayed, was not found to increase the rate of endophthalmitis.

EVALUATION OF SEGMENTAL RETINAL ARTERITIS WITH OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To describe the vascular anatomy and intraluminal flow characteristics of segmental retinal arteritis (SRA) using structural and angiographic optical coherence tomography (OCT). METHODS: Retrospective case series of consecutive patients presenting with SRA. All patients were evaluated at presentation with fundus photography, spectral domain OCT, and OCT angiography. One patient was imaged with dense B-scan OCT angiography. RESULTS: Three eyes of three male patients were evaluated. All examinations were consistent with reactivation of ocular toxoplasmosis with an area of active retinochoroiditis adjacent to a focal chorioretinal scar. Spectral domain OCT through areas of SRA noted on clinical examination demonstrated areas of hyperreflectivity circumscribing the affected vessel with a normoreflective lumen. Optical coherence tomography angiography and dense B-scan OCT angiography demonstrated narrowing of the intraluminal flow signal that correlated with areas of segmental hyperreflectivity on spectral domain OCT. Vascular sections proximal and distal to areas of SRA showed normal flow signal. CONCLUSION: Vessels with SRA demonstrated hyperreflectivity highlighting the vessel wall on spectral domain OCT. Optical coherence tomography angiography showed narrowing of the flow signal within these segments suggesting reduced lumen diameter. Coupling these finding with previous indocyanine green imaging findings in SRA, the collective data suggest the plaques are localized within the vessel wall to either the endothelium or the muscular tunica media without occlusion of the vessel lumen.

ASSESSING THE ABILITY OF PREOPERATIVE QUANTITATIVE SPECTRAL-DOMAIN OPTICAL COHERENCE TOMOGRAPHY CHARACTERISTICS TO PREDICT VISUAL OUTCOME IN IDIOPATHIC MACULAR HOLE SURGERY.

PURPOSE: To determine which spectral domain optical coherence tomography biomarkers of idiopathic macular hole (MH) correlate with the postoperative best-corrected visual acuity (BCVA) in anatomically closed MH. METHODS: Retrospective analysis of spectral domain optical coherence tomography scans of 44 patients presenting with MH followed for a mean of 17 months. Widths of MH aperture, base, and ellipsoid zone disruption were calculated from presenting foveal spectral domain optical coherence tomography B-scans. Macular hole base area and ellipsoid zone disruption area were calculated through the custom in-house software. RESULTS: Poorer postoperative BCVA correlated with increased preoperative choroidal hypertransmission (r = 0.503, P = 0.0005), minimum diameter (r = 0.491, P = 0.0007), and base diameter (r = 0.319, P = 0.0348), but not with preoperative ellipsoid zone width (r = 0.199, P = 0.2001). Applying en-face analysis, the BCVA correlated weakly with preoperative ellipsoid zone loss area (r = 0.380, P = 0.013), but not with preoperative MH base area (r = 0.253, P = 0.1058). CONCLUSION: Increased MH minimum diameter, base diameter, base area, and choroidal hypertransmission are correlated with a poorer postoperative BCVA. Ellipsoid zone loss measurements were not consistently correlated with a BCVA. Choroidal hypertransmission width may be an easy-to-visualize predictive imaging biomarker in MH surgery.

Antimicrobial guide to posterior segment infections.

PURPOSE: This review article is meant to serve as a reference guide and to assist the treating physician in making an appropriate selection and duration of an antimicrobial agent. METHODS: Literature review. RESULTS: Infections of the posterior segment require prompt medical or surgical therapy to reduce the risk of permanent vision loss. While numerous options exist to treat these infections, doses and alternative therapies, especially with contraindications for first-line therapy, are often elusive. Antimicrobial agents to treat posterior segment infections can be administered via various routes, including topical, intravitreal, intravenous, and oral. CONCLUSIONS: Although there are many excellent review articles on the management of endophthalmitis, we take the opportunity in this review to comprehensively summarize the appropriate antimicrobial regimen of both common and rare infectious etiologies of the posterior segment, using evidence from clinical trials and large case series.

TENON CAPSULE-VITREOUS CAVITY FISTULA AFTER HYDROGEL SCLERAL BUCKLE REMOVAL.

PURPOSE: To report a rare case of vitreous cavity-Tenon capsule fistula formation after removal of a symptomatic hydrogel scleral buckle. METHODS: Case report. RESULTS: A 43-year-old man presented with chronic headache and involuntary gaze deviation for over 1 year after hydrogel scleral buckle surgery 25 years prior. After removal of the scleral buckle, the patient developed a fluid-filled inflation of the buckle capsule, surrounding a previously noted area of severe scleral thinning. Ocular ultrasonography suggested a fistulous connection between the vitreous cavity and the sub-Tenon space in the area of scleral thinning. There was resolution of diplopia and headache postoperatively, with stability of the fluid collection on clinical examination. Because of high risk of further surgery and resolution of the patient's symptoms, conservative management was elected. CONCLUSION: This is the first report, to the best of our knowledge, of Tenon capsule-vitreous cavity fistula formation after scleral buckle explantation. Because of innate ability to expand, as well as tendency to become friable, hydrogel buckles have a higher risk of requiring removal and of complications from explantation, respectively. Our patient experienced relief of symptoms, without complication from the fistula, and was successfully managed conservatively.

Smartphone-based fundus photography for screening of plus-disease retinopathy of prematurity.

BACKGROUND: Inadequate screening of treatment-warranted retinopathy of prematurity (ROP) can lead to devastating visual outcomes. Especially in resource-poor communities, the use of an affordable, portable, and easy to use smartphone-based non-contact fundus photography device may prove useful for screening for high-risk ROP. This study evaluates the feasibility of screening for high-risk ROP using a novel smartphone-based fundus photography device, RetinaScope. METHODS: Retinal images were obtained using RetinaScope on a cohort of prematurely born infants during routine examinations for ROP. Images were reviewed by two masked graders who determined the image quality, the presence or absence of plus disease, and whether there was retinopathy that met predefined criteria for referral. The agreement between image-based assessments was compared to the gold standard indirect ophthalmoscopic assessment. RESULTS: Fifty-four eyes of 27 infants were included. A wide-field fundus photograph was obtained using RetinaScope. Image quality was acceptable or excellent in 98% and 95% of cases. There was substantial agreement between the gold standard and photographic assessment of presence or absence of plus disease (Cohen's κ = 0.85). Intergrader agreement on the presence of any retinopathy in photographs was also high (κ = 0.92). CONCLUSIONS: RetinaScope can capture digital retinal photographs of prematurely born infants with good image quality for grading of plus disease.

Smartphone-Based, Rapid, Wide-Field Fundus Photography for Diagnosis of Pediatric Retinal Diseases.

PURPOSE: An important, unmet clinical need is for cost-effective, reliable, easy-to-use, and portable retinal photography to evaluate preventable causes of vision loss in children. This study presents the feasibility of a novel smartphone-based retinal imaging device tailored to imaging the pediatric fundus. METHODS: Several modifications for children were made to our previous device, including a child-friendly 3D printed housing of animals, attention-grabbing targets, enhanced image stitching, and video-recording capabilities. Retinal photographs were obtained in children undergoing routine dilated eye examination. Experienced masked retina-specialist graders determined photograph quality and made diagnoses based on the images, which were compared to the treating clinician's diagnosis. RESULTS: Dilated fundus photographs were acquired in 43 patients with a mean age of 6.7 years. The diagnoses included retinoblastoma, Coats' disease, commotio retinae, and optic nerve hypoplasia, among others. Mean time to acquire five standard photographs totaling 90-degree field of vision was 2.3 ± 1.1 minutes. Patients rated their experience of image acquisition favorably, with a Likert score of 4.6 ± 0.8 out of 5. There was 96% agreement between image-based diagnosis and the treating clinician's diagnosis. CONCLUSIONS: We report a handheld smartphone-based device with modifications tailored for wide-field fundus photography in pediatric patients that can rapidly acquire fundus photos while being well-tolerated. TRANSLATIONAL RELEVANCE: Advances in handheld smartphone-based fundus photography devices decrease the technical barrier for image acquisition in children and may potentially increase access to ophthalmic care in communities with limited resources.

Ocular Manifestations of Cutis Marmorata Telangiectatica Congenita.

PURPOSE: To describe the range of ocular manifestations in cutis marmorata telangectatica congenita (CMTC). DESIGN: Multicenter, retrospective, nonconsecutive case series. PARTICIPANTS: Patients with a diagnosis of CMTC referred for ophthalmologic evaluation between January 1, 2015, and December 31, 2018. METHODS: Evaluation of ocular findings at presentation, systemic manifestations suggestive of a diagnosis of CMTC, genetic testing, and visual outcomes after treatment. MAIN OUTCOME MEASURES: Visual acuity, findings on ophthalmoscopy, and results of fluorescein angiography. RESULTS: Nine patients with CMTC diagnosed clinically based on stereotypical cutaneous vascular malformations were included. The median age at presentation was 8 weeks (range, 2 weeks-4 years). Six patients were female and 3 were male. Avascular retina was identified on dilated fundus examination, fluorescein angiography, or both in 11 eyes of 6 patients. Retinal neovascularization was present bilaterally in 2 patients at presentation. One patient demonstrated retinal venous tortuosity, and another patient showed mild straightening of nasal retinal vessels in both eyes. Two patients (2 eyes) demonstrated retinal detachment (RD). Both were managed surgically. One infant demonstrated RD, whereas the other child showed extensive neovascularization and later progressed to combined tractional-rhegmatogenous detachment. A unique constellation of lacy peripheral capillary anomalies with prominent terminal vascular bulbs was noted in 3 patients. Granular pigment abnormalities were noted in the macula in 5 patients. Two patients demonstrated glaucoma, 1 requiring surgical intervention. Two patients demonstrated features of Adams-Oliver syndrome, with genetic testing identifying a Notch1 mutation in 1 patient. CONCLUSIONS: Retinal vascular abnormalities in CMTC may occur more frequently than recognized previously. Given the variability of ocular involvement and the potential for rapidly progressive retinal vascular abnormalities and development of RD, complete ophthalmologic evaluation including measurement of intraocular pressure, gonioscopy, dilated fundus examination, and fluorescein angiography is recommended in infants with suspected CMTC shortly after birth. The distinct pattern of lacy capillary anomalies with prominent terminal bulbs seen in CMTC has not been described in other syndromes of vascular dysgenesis. Therefore, ophthalmic examination may be a valuable method to distinguish CMTC from other disorders demonstrating similar dermatologic and systemic manifestations.