The 0.19-mg Fluocinolone Acetonide Implant for the Treatment of Diabetic Macular Edema: An Expert Consensus.

BACKGROUND AND OBJECTIVE: To better understand the level of agreement among retina specialists on the role of inflammation in diabetic retinopathy (DR) and diabetic macular edema (DME), and the use of 0.19-mg fluocinolone acetonide (FAc) implant in DME treatment, a consensus survey was drafted and disseminated to retina specialists across the United States. MATERIALS AND METHODS: Using the modified Delphi method, a list of 12 consensus statements were generated by the coauthors based on short-answer responses to an initial survey. In total, 56 retina specialists completed the entire consensus survey. Except for two multiple-choice questions, there were 10 consensus statements that used a modified Likert scale to indicate their level of agreement to the statement: Agree = 3, Mostly Agree = 2, Mostly Disagree = 1, Disagree = 0. Percentage agreement and 95% confidence intervals (CIs) were calculated, and a consensus threshold was set at > 80% agreement for each statement. RESULTS: Seven of 10 consensus statements using the modified Likert scale reached consensus, including those on the role of inflammation in pathophysiology of DR/DME, injection burden and patient adherence, and efficacy and safety of the FAc implant. The remaining three statements displayed high agreement with average scores > 80%, but the 95% CIs were below threshold. These included the impact of the FAc implant on DR progression, FAc as baseline therapy for DME, and the effectiveness of the steroid challenge to mitigate intraocular pressure risk after FAc use. Two multiple-choice questions focused on clinical situations in which corticosteroids would be used as baseline therapy for DME (pseudophakic eye [73%], recent stroke/myocardial infarction [66%], and pregnancy/breastfeeding [66%]) and which delivery route satisfies the steroid challenge for the FAc implant (intravitreal [100%], sub-tenon/periocular [73%], and topical [57%]). CONCLUSIONS: Physicians highly agreed on the role of inflammation in pathophysiology of DR/DME, injection burden and patient adherence, and efficacy and safety of the FAc implant. However, full consensus was not found on the impact of the FAc implant on DR progression, FAc as baseline therapy for DME, and the effectiveness of the steroid challenge to mitigate intraocular pressure risk after FAc use. [Ophthalmic Surg Lasers Imaging Retina. 2023;54(3):166-173.].

PERSISTENT PLACOID MACULOPATHY IN A PATIENT WITH HIGH MYOPIA.

PURPOSE: To describe a case of persistent placoid maculopathy in a patient with high myopia. METHODS: Interventional case report. RESULTS: A 59-year-old white man with high myopia presented with blurriness in the left eye. Vision was 20/20 bilaterally. Optical coherence tomography showed subretinal thickening and fluid without definitive leakage on fluorescein angiography after which anti-vascular endothelial growth factor (anti-VEGF) therapy was initiated. The patient was diagnosed with persistent placoid maculopathy based on multimodal imaging and clinical response. His disease course was characterized by multiple bilateral recurrences despite active treatment. At final visit (23 months after presentation), the vision was 20/20 in the right eye and 20/25 in the left eye, and the disease remained quiescent on immunomodulating therapy. CONCLUSION: Prompt initiation of anti-VEGF injections and immunosuppression resulted in disease control and preservation of vision in both eyes for almost 2 years.

BETA-PERIPAPILLARY ATROPHY AND GEOGRAPHIC ATROPHY IN THE COMPARISON OF AGE-RELATED MACULAR DEGENERATION TREATMENTS TRIALS.

PURPOSE: To determine associations between beta-peripapillary atrophy (B-PPA) and incidence and growth of geographic atrophy (GA) in eyes treated with anti-vascular endothelial growth factor agents in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT). METHODS: We included 245 cases with incident GA and 245 controls matched by baseline demographics and characteristics associated with development of GA in the CATT. Baseline color images were graded for the type of B-PPA, defined as presence of hypopigmentation with visible choroidal vessels and sclera that is adjacent to the optic disk. Beta-peripapillary atrophy was further classified as scleral ring, sclera, sclera/choroidal blood vessels, or combination. Areas of each type of B-PPA and the circumferential extent of B-PPA were measured. RESULTS: Beta-peripapillary atrophy was present in 58% of eyes developing GA and in 52% without GA (P = 0.17). The greater circumferential extent of sclera/choroidal blood vessels B-PPA in relation to the optic disk was associated with incident GA (P = 0.02) and the GA size at first observation (P = 0.047). Beta-peripapillary atrophy was not associated with GA growth rates (P>0.05). Patients without B-PPA had a higher number of GA-associated risk alleles of ARMS2 (P = 0.0003) and HTRA1 (P = 0.001). CONCLUSION: The extent of sclera/choroidal blood vessel B-PPA was associated with the GA incidence and size but not with the growth rate in eyes treated for neovascular age-related macular degeneration. Beta-peripapillary atrophy and GA may share some common pathophysiologic pathways unrelated to the GA-associated risk alleles evaluated.

Association of Opioids With Incisional Ocular Surgery.

IMPORTANCE: Opioid abuse has been declared a public health emergency. Currently, little is known about the association between opioids and ocular surgery. OBJECTIVE: To characterize rates of filled opioid prescriptions after incisional ocular surgeries. DESIGN, SETTING, AND PARTICIPANTS: This cohort study included patients with incisional ocular surgeries within a large national US insurer's administrative medical claims database. All incisional ocular surgeries from January 2000 through December 2016 were evaluated. An opioid prescription was eligible if it occurred from 1 day before to 7 days after a surgery. Any surgery on a patient who was younger than 18 years, had more than 30 consecutive days of an opioid prescription in the prior 6 months, or had less than 6 months of data in the database prior to surgery was excluded. Data analysis occurred from May 2018 through November 2018. MAIN OUTCOMES AND MEASURES: The rate of opioid prescriptions filled for all incisional ocular surgeries from 2000 through 2016. Primary analysis looked at the rate of filled opioid prescriptions for each ophthalmic subspecialty surgery over time. Secondary analysis assessed which patient or surgical characteristics (ie, age, sex, race/ethnicity, geographic locations, yearly income, educational level, and type of eye surgery) were associated with filling an opioid prescription. Multivariate logistic regression using generalized estimating equations was used to determine odds ratios (ORs) of filling an opioid prescription. RESULTS: A total of 2 407 962 incisional ocular surgeries were included, of which 45 776 (1.90%) were associated with an opioid prescription. The rate of filled opioid prescriptions varied considerably over time, with the lowest rate occurring in the 2000-2001 cohort year (671 of 45 776 [1.24%]) and the highest in 2014 (5559 of 45 776 [2.51%]). An increasing trend was seen over the course of the study (2000-2001: 671 of 45 776 [1.24%]; 2016: 5851 of 45 776 [2.07%]; P < .001). Multivariate logistic regression showed that year of surgery was significantly associated with filling an opioid prescription, with the highest odds in 2014 (OR, 3.71 [95% CI, 3.33-4.1]), 2015 (OR, 3.33 [95% CI, 2.99-3.70]), and 2016 (OR, 3.27 [95% CI, 2.94-3.63]) compared with 2000 to 2001 (P < .001). CONCLUSIONS AND RELEVANCE: These findings suggest the rate of filled opioid prescriptions are increasing for all types of incisional ocular surgery over time. Given the ongoing national opioid epidemic, understanding patterns of use can help in reversing the epidemic.

ACUTE EXUDATIVE PARANEOPLASTIC POLYMORPHOUS VITELLIFORM MACULOPATHY DURING VEMURAFENIB AND PEMBROLIZUMAB TREATMENT FOR METASTATIC MELANOMA.

PURPOSE: To describe a patient with BRAF mutation-positive cutaneous melanoma who developed acute exudative polymorphous vitelliform maculopathy during vemurafenib and pembrolizumab treatment for metastatic melanoma. METHODS: Retrospective case report documented with wide-field fundus imaging, spectral domain optical coherence tomography, and fundus autofluorescence imaging. RESULTS: A 55-year-old woman with bilateral ductal breast carcinoma and BRAF mutation-positive metastatic cutaneous melanoma complained of bilateral blurred vision within 5 days of starting vemurafenib (BRAF inhibitor). She had been on pembrolizumab (program death receptor antibody) and intermittently on dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor), and had a normal ophthalmologic examination. On presentation three weeks after the introduction of vemurafenib, her visual acuity had declined to 20/40 in both eyes. Her examination showed diffuse elevation of the fovea with multifocal yellow-white, crescent-shaped subretinal deposits within the macula of both eyes and bilateral neurosensory retinal detachments by spectral domain optical coherence tomography. Discontinuation of vemurafenib and introduction of difluprednate and dorzolamide led to a gradual resolution (over four months) of the neurosensory detachments with recovery of vision. CONCLUSION: This case report suggests that acute exudative polymorphous vitelliform maculopathy may be directly associated with the use of BRAF inhibitors as treatment for metastatic cutaneous melanoma, or indirectly by triggering autoimmune-paraneoplastic processes. Future identification of similar associations is required to unequivocally link vemurafenib and/or pembrolizumab to acute exudative polymorphous vitelliform maculopathy in metastatic melanoma.

Anterior chamber fibrinoid syndrome after cataract extraction in a patient on ibrutinib for B-cell chronic lymphocytic leukemia: a case report and review of the literature.

BACKGROUND: Ibrutinib is a tyrosine kinase inhibitor commonly used in patients with chronic lymphocytic leukemia. Based on the published literature, it has a very sound ophthalmologic safety profile. In the following, we describe a case of anterior chamber fibrinoid syndrome in a patient on ibrutinib for B-cell chronic lymphocytic leukemia after uncomplicated cataract extraction. CASE PRESENTATION: A 75-year-old white man with B-cell chronic lymphocytic leukemia on ibrutinib therapy and without significant past ocular history presented 1 day after uncomplicated phacoemulsification with in-the-bag intraocular lens implantation with multiple, discrete, pigmented cords in the anterior chamber. His vision was 20/100 and intraocular pressure was 43 mmHg. There was no hypopyon, hyphema, or cellular reaction. The dilated fundus examination was unremarkable. He was diagnosed as having fibrinoid syndrome and started on topical prednisolone, brimonidine, timolol-dorzolamide, and orally administered acetazolamide. Within 2 weeks, the fibrin cords disappeared completely, vision improved to 20/30, and the intraocular pressure normalized off all medications. CONCLUSIONS: The precise etiology of fibrinoid syndrome remains unclear. This is the first case of fibrinoid syndrome in a patient on ibrutinib, which is known to cross the blood-brain barrier and induce intraocular changes. It is important to differentiate this syndrome from toxic anterior segment syndrome and endophthalmitis, and to initiate appropriate treatment. The fibrin bands tend to be exquisitely sensitive to topical steroids and to resolve within a few weeks without sequelae.

PERSISTENT PLACOID MACULOPATHY: A Systematic Review.

PURPOSE: To review the literature on persistent placoid maculopathy. METHODS: Several databases were searched for all years for "persistent placoid maculopathy." RESULTS: A total of 21 unique patients were identified (most commonly Caucasian men in their 50s and 60s). Mean ± SD age at time of presentation was 58.6 ± 6.9 years of age, and follow-up time was 29.2 ± 51.9 months. Thirty-three (79%) eyes had subjective symptoms on presentation. Five (24%) patients presented with a prodrome, and four (19%) patients had vitreous cell. Mean ± SD logarithm of minimal angle of resolution presenting versus final vision was 0.48 ± 0.50 (Snellen equivalent, 20/60) versus 0.63 ± 0.52 (Snellen equivalent, 20/84). Systemic inflammation and autoimmune disease were associated with worse presenting and final vision. Persistent placoid maculopathy characteristic imaging features that aid in diagnosing this rare clinical entity include the following: 1) plaque-like hypopigmented, white/yellowish foveal/perifoveal lesions on color fundus photography; 2) early hypofluorescence and late "fill-in" or staining on fluorescein angiography; 3) persistent hypocyanescence on indocyanine green angiography; and 4) choriocapillaris hyposignal on optical coherence tomography angiography. Choroidal neovascularization was present in 50% of eyes, with 62% diagnosed at presentation. Although choroidal neovascularization is typically responsive to anti-vascular endothelial growth factor injections, it is associated with poor visual outcome. Systemic steroids are generally used as first-line agents with addition of other immunomodulatory medications if the disease is refractory or recurrent. CONCLUSION: Precise disease pathophysiology of persistent placoid maculopathy has not been elucidated but most probably relates to selective choriocapillaris hypoperfusion/ischemia/vasculitis. Combination of anti-vascular endothelial growth factor injections and immunosuppressive medications may be effective in controlling disease activity and limiting development of sight-threatening complications.

Management of Presumed Endogenous Fungal Endophthalmitis in a Child With Acute Lymphoblastic Leukemia.

The authors describe a case of presumed endogenous fungal endophthalmitis in an immunocompetent pediatric patient with acute lymphoblastic leukemia. A 15-year-old boy with a history of high-risk B-cell acute lymphoblastic leukemia status post-chemotherapy presented with acute changes in vision in his left eye. Fundus examination revealed a white bi-lobed chorioretinal lesion with overlying vitritis and associated subretinal fluid. Magnetic resonance imaging of the brain revealed small ring-enhancing lesions in the right parietal and left occipital lobes. Blood, cerebrospinal fluid, aqueous, and vitreous cultures were all negative. Bone marrow and vitreous cytology were negative for malignant cells. The patient was treated for presumed fungal endophthalmitis with systemic and intravitreal voriconazole, followed by pars plana vitrectomy with intravitreal voriconazole and amphotericin B injections. The chorioretinal lesion resolved and visual acuity recovered to 20/20. Chorioretinal infiltrates in a patient with leukemia may require treatment even in the absence of a definitive diagnostic test result. Intervention should be guided by risk analysis and clinical judgment. [J Pediatr Ophthalmol Strabismus. 2017;54:e42-e46.].

Intravitreal Bevacizumab for the Treatment of Vitreous Hemorrhage Due to Proliferative Diabetic Retinopathy.

PURPOSE: To evaluate the outcomes of intravitreal bevacizumab (IVB) use in patients with a vitreous hemorrhage (VH) secondary to proliferative diabetic retinopathy (PDR). DESIGN: Retrospective, interventional case series. METHODS: Patients who presented to Scheie Eye Institute between January 2008 and January 2015 with a new VH secondary to PDR and treated with IVB were included. Exclusion criteria consisted of IVB treatment prior to the study, a history of pars plana vitrectomy (PPV), and less than 1 year of follow-up. Outcomes of interest were additional treatments including PPV, injections, and panretinal photocoagulation (PRP), as well as visual acuity at baseline and at 1 year. RESULTS: Of the 111 eligible eyes, 55 (49.5%) had PRP, 35 (31.6%) were managed with injections alone, and 21 (18.9%) had PPV after 1 year. The overall average number of injections during this time was 2 (range, 1-9), and 13 (11.7%) eyes were managed with a single injection alone. Of the 69 eyes with 2 years of follow-up, 43 (62.3%) had PRP, 16 (23.2%) were treated with injections alone, and 10 (14.5%) had PPV. CONCLUSIONS: This study underscores the potentially important role that IVB injections have in the management of patients with VH secondary to PDR. The results indicate that a proportion of patients may be treated with a minimal amount of intervention requiring 1 or 2 anti-vascular endothelial growth factor injections only. Also, the rate of PPV at 2 years (27.9%, n = 31) suggests that most patients may be managed nonsurgically.

Bilateral Cavernous Sinus Thrombosis in a Patient with Tacrolimus-Associated Posttransplant Thrombotic Microangiopathy.

Purpose To report a case of bilateral cavernous sinus thrombosis (CST) in a patient with tacrolimus-associated posttransplant thrombotic microangiopathy. Methods Case report. Results An 8-year-old boy with a medical history of orthotopic heart transplant, posttransplant lymphoproliferative disease, and recurrent infections was hospitalized for nausea, vomiting, and diarrhea. His ocular history included accommodative esotropia, hyperopia with astigmatism, Molluscum contagiosum lid lesions, and idiopathic intracranial hypertension. Shortly after presentation, he developed increased intraocular pressure, an afferent pupillary defect, a layered hyphema, and tense proptosis of the left globe requiring an emergent canthotomy and cantholysis. Over the next month, the patient's hospital course included subdural and subarachnoid hemorrhage, temporal lobe stroke, serotonin syndrome, bilateral CST, and systemic microangiopathy. After an extensive workup, a diagnosis of tacrolimus-associated thrombotic microangiopathy was made. At this point, vision was 20/20 in the right eye and light perception in the left eye. Eight months after the canthotomy and cantholysis, the patient's vision in the left eye deteriorated to no light perception and remained so after 13 months of follow-up. Conclusions An idiosyncratic drug reaction should be considered in the differential diagnosis of CST, especially in a patient on calcineurin inhibitors after solid organ transplant without sinus disease or orbital cellulitis.

COMPREHENSIVE REVIEW OF GOLF-RELATED OCULAR INJURIES.

PURPOSE: The authors aimed to analyze the causes and outcomes of golf-related ocular injuries in this retrospective meta-analysis, literature review, and original case series. METHODS: Forty-one articles identified by PubMed search resulted in 11 included studies yielding 102 subjects. Included articles described all ocular golf injuries that presented to an institution during a determined period. Eight factors were analyzed: age, sex, location and mechanism of injury, protective eyewear use, resulting open-globe injury, resulting enucleation, and visual acuity changes. RESULTS: No subjects wore adequate protective eyewear. Significantly more subjects were injured by golf balls (72%) than golf clubs (27%) or foreign body (1%) (P < 0.0001). The ratio of golf ball to club injuries was significantly higher in adults (92%) than in children (23%) (P < 0.0001). Forty-seven of 93 (51%) injuries resulted in an open globe, whereas 27/82 (33%) injuries resulted in enucleation. The mean ± SD logMAR visual acuity improved by -0.641 ± 0.745 after treatment (>6 lines of improvement; P = 0.0001). CONCLUSION: Reported ocular golf injuries occur less frequently than other ocular sports injuries, but may result in devastating outcomes. Supervision of children using golf equipment should be encouraged.

Chronic Non-infectious Uveitis in Patients with Juvenile Idiopathic Arthritis.

PURPOSE: To describe clinical findings and analyze treatment evolution of chronic, non-infectious uveitis in patients with juvenile idiopathic arthritis (JIA). METHODS: A total of 82 patients (147 eyes) with JIA-related uveitis treated for ≥2 months were included (78% females; 79% bilateral uveitis; 74% anterior uveitis). Outcome measures were visual acuity (VA), inflammation control, side-effects, and surgical procedures. RESULTS: Mean ± SD age at diagnosis was 4.9 ± 3.8 years; mean ± SD follow-up time was 8.7 ± 7.8 years. Mean VA did not significantly change throughout the study. Three (2%) eyes resulted in no light perception (NLP) vision. Thirty (37%) patients underwent 69 procedures. In total, 41 (50%) patients achieved inflammation control. TNF-α inhibitors were significantly associated with inflammation control. Seven (8.5%) patients stopped treatment due to side-effects. CONCLUSIONS: JIA is a cause of significant ocular morbidity. TNF-α inhibitor use was associated with inflammation control. Prospective, randomized, double blind clinical trials in this regard are warranted.

SPONTANEOUS RESOLUTION OF MACULAR EPIRETINAL MEMBRANES AFTER FLUORESCEIN POTENTIATED ARGON LASER TREATMENT OF VON HIPPEL-LINDAU ASSOCIATED RETINAL HEMANGIOMAS: CASE REPORT AND REVIEW OF LITERATURE.

PURPOSE: To illustrate spontaneous resolution of macular epiretinal membranes and inactivation of retinal hemangioma exudation after fluorescein potentiated argon laser treatment of bilateral capillary hemangiomas in a patient with a de novo heterozygous deletion in Exon 2 of the von Hippel-Lindau gene. METHODS: Interventional case report. RESULTS: A 23-year-old man with subjective complaints of blurry vision, photophobia, and glare. On presentation, visual acuity was 20/20 in the right eye and 20/25 in the left eye with metamorphopsia. On the basis of bilateral retinal hemangiomas on clinical examination and characterization with multimodal imaging, a diagnosis of von Hippel-Lindau disease was made. Genetic testing identified a de novo, disease-causing heterozygous deletion in Exon 2 of the von Hippel-Lindau gene. The patient underwent 4 sessions of fluorescein potentiated 532 nm argon green laser treatment directed at retinal hemangiomas. No adverse sequelae of laser treatment were noted. Seven months after the initial presentation, the patient's vision was 20/20 in both eyes with interval resolution of metamorphopsia. There was spontaneous resolution of a macular epiretinal membrane with normalization of the macular retinal microstructure. The retinal hemangiomas in both eyes appeared inactive, and no new lesions were noted. CONCLUSION: Fluorescein potentiated argon laser successfully treated bilateral retinal hemangiomas in our patient with von Hippel-Lindau disease. Additional studies to characterize the full clinical potential of fluorescein potentiated argon laser therapy may be warranted.

Lamotrigine-induced tubulointerstitial nephritis and uveitis-atypical Cogan syndrome.

PURPOSE: To report a case of lamotrigine-induced tubulointerstitial nephritis and uveitis (TINU)-atypical Cogan syndrome. METHODS: Case report. RESULTS: A 16-year-old boy with traumatic brain injury and seizures presented to the emergency department with facial swelling, rash, and back pain several days after increasing lamotrigine dose secondary to a breakthrough seizure. Creatinine, urine ß2 microglobulin, and eosinophils were elevated. Antinuclear antibodies, antineutrophil cytoplasmic antibodies, angiotensin-converting enzyme, and complement were normal. Renal biopsy showed acute granulomatous tubulointerstitial nephritis. Lamotrigine was discontinued, intravenous steroids were initiated, and the patient was discharged on Ativan and prednisone. Subsequently, he was diagnosed with bilateral anterior uveitis (vision 20/30 bilaterally) and started on prednisolone and cyclopentolate. Two months later, he developed a branch retinal artery occlusion in the right eye (vision 20/70) and bilateral ocular hypertension for which timolol-brimonidine and dorzolamide were added. Neuroimaging and hypercoagulability workup was unremarkable. Vision and intraocular pressure improved, while uveitis remained recalcitrant. Several months later, the patient developed central serous retinopathy in the right eye (vision 20/30). Prednisone was stopped but restarted due to methotrexate intolerance. A month later, he reported dizziness and was diagnosed with severe bilateral sensorineural hearing loss. Brain magnetic resonance imaging showed foci of perivascular, subcortical, and cochlear enhancement. Transtympanic Decadron injections and infliximab infusions were initiated. At the final visit, vision remained at 20/30 with trace anterior chamber reaction bilaterally while on timolol-brimonidine, dorzolamide, and prednisolone. CONCLUSIONS: An idiosyncratic drug reaction should be considered in the differential diagnosis of TINU-atypical Cogan syndrome.

The Use of Ozurdex (Dexamethasone Intravitreal Implant) During Anterior Segment Surgery in Patients with Chronic Recurrent Uveitis.

PURPOSE: To describe the outcomes of concurrent Ozurdex implantation during anterior segment surgery in patients with chronic recurrent uveitis. METHODS: Retrospective chart review. Data recorded from preoperative and 1-, 3-, and 6-month postoperative visits included visual acuity, intraocular pressure (IOP), medications, and clinical examination findings of inflammation. RESULTS: Twelve patients (12 eyes) with chronic, recurrent noninfectious uveitis undergoing cataract extraction (n=9) or intraocular lens (IOL) explantation (n=3) were included. Mean duration of follow-up after Ozurdex implantation was 12.9 months. There was a significant reduction (n=10, P=0.02) in the average number of inflammation recurrences 6 months before surgery compared to 6 months after surgery with Ozurdex in affected eyes. IOP remained stable in the postoperative period. One patient undergoing anterior chamber IOL (ACIOL) explantation experienced migration of Ozurdex into the anterior chamber resulting in corneal edema that resolved after 1 month. CONCLUSIONS: Ozurdex safely and effectively controlled postoperative inflammation in eyes with chronic recurrent uveitis when concurrently implanted during anterior segment surgery in our patients. Caution should be exercised in cases of IOL explantation, as Ozurdex use is now contraindicated in eyes with posterior capsule rupture and ACIOLs.