Total venous nature of retinal deep capillary plexus inferred by continuity of prominent middle limiting membrane sign in optical coherence tomography.

This study aimed to theoretically identify the vascular nature of the deep capillary plexus (DCP) by examining patients presenting with both paracentral acute middle maculopathy (PAMM) and prominent middle limiting membrane (p-MLM) sign and p-MLM sign alone in spectral-domain optical coherence tomography (SD-OCT). A retrospective review of the medical records of patients with retinal vein or artery occlusion from two tertiary medical centers was performed. Consecutive patients with a clinical diagnosis of all categories of retinal artery occlusion (RAO) and retinal vein occlusion (RVO) (branch or central and ischemic or non-ischemic) who had undergone SD-OCT imaging from January 2015 to May 2020 were recruited and their p-MLM signs and PAMM lesions were assessed. We included 118 patients who presented with p-MLM sign with or without PAMM lesions. Amon them, 40 were female and 78 were male, with a mean age of 61.1 years. Of the 109 patients with both p-MLM sign and PAMM lesions, 23 had branch RAO, two had branch RVO, 67 had central RAO, 13 had central RVO, and four had a combination of central RAO and central RVO. All nine patients with the p-MLM sign alone had central RVO accompanied by cystoid macular edema. In all the enrolled patients, the hyperreflective lines of the p-MLM sign were continuous, regardless of the type of PAMM lesions. In conclusion, when PAMM and p-MLM sign are examined together, further proof regarding the possible complete venous nature of the vasculature of the retinal DCP might be speculated.

Ocular side effects of novel anti-cancer biological therapies.

To examine the ocular side effects of selected biological anti-cancer therapies and the ocular and systemic prognosis of patients receiving them. We retrospectively reviewed all medical records of patients who received biological anti-cancer treatment from 1/2012 to 12/2017 and who were treated at our ocular oncology service. The following data was retrieved: primary malignancy, metastasis, type of biological therapy, ocular side effects, ophthalmic treatment, non-ocular side effects, and ocular and systemic disease prognoses. Twenty-two patients received biological therapies and reported ocular side effects. Eighteen patients (81.8%) had bilateral ocular side effects, including uveitis (40.9%), dry eye (22.7%), and central serous retinopathy (22.7%). One patient (4.5%) had central retinal artery occlusion (CRAO), and one patient (4.5%) had branch retinal vein occlusion (BRVO). At the end of follow-up, 6 patients (27.27%) had resolution of the ocular disease, 13 patients (59.09%) had stable ocular disease, and 3 patients (13.64%) had progression of the ocular disease. Visual acuity improved significantly at the end of follow-up compared to initial values. Eighteen patients (81.8%) were alive at study closure. Biological therapies can cause a wide range of ocular side effects ranging from dry eye symptoms to severe pathologies that may cause ocular morbidity and vision loss, such as uveitis, CRAO and BRVO. All patients receiving biological treatments should be screened by ophthalmologists before treatment, re-screened every 4-6 months during treatment, and again at the end of treatment. Patients on biological treatment who have ocular complaints should be urgently referred to ocular consultation for early identification and early intervention.

Aqueous Fibronectin Correlates With Severity of Macular Edema and Visual Acuity in Patients With Branch Retinal Vein Occlusion: A Proteome Study.

Purpose: Large-scale protein analysis may bring important insights into molecular changes following branch retinal vein occlusion (BRVO). Using proteomic techniques this study compared aqueous humor samples from patients with BRVO to age-matched controls. Methods: Aqueous humor samples from treatment naive patients with BRVO complicated by macular edema (n = 19) and age-matched controls (n = 18) were analyzed with label-free quantification nano liquid chromatography - tandem mass spectrometry (LFQ nLC-MS/MS). The severity of macular edema was measured as central retinal thickness (CRT) with optical coherence tomography. Control samples were obtained prior to cataract surgery. Proteins were filtered by requiring quantification in at least 50% of the samples in each group without imputation of missing values. Significantly changed proteins were identified with a permutation-based calculation with a false discovery rate at 0.05. Results: In BRVO, 52 proteins were differentially expressed. Regulated proteins were involved in cell adhesion, coagulation, and acute-phase response. Apolipoprotein C-III, complement C3, complement C5, complement factor H, fibronectin, and fibrinogen chains were increased in BRVO and correlated with CRT. Fibronectin also correlated with best corrected visual acuity (BCVA) and vascular endothelial growth factor (VEGF). Monocyte differentiation antigen CD14 (CD14) and lipopolysaccharide-binding protein (LBP) were upregulated in BRVO. Contactin-1 and alpha-enolase were downregulated in BRVO and correlated negatively with CRT. Conclusions: Multiple proteins, including complement factors, fibrinogen chains, and apolipoprotein C-III, correlated with CRT, indicating a multifactorial response. Fibronectin correlated with BCVA, CRT, and VEGF. Fibronectin may reflect the severity of BRVO. The proinflammatory proteins CD14 and LBP were upregulated in BRVO.

Hyperreflective foci in diabetic macular edema with serous retinal detachment: association with dyslipidemia.

AIMS: Hyperreflective foci (HF), detected in the retina of diabetic patients, suggest the presence of microglial activation and migration, while controversies still remain for the origin of HF to be precursors of hard exudates. We investigated the presence of HF and their association with dyslipidemia in serous retinal detachment (SRD)-type diabetic macular edema (DME). METHODS: Forty-two eyes in 42 patients with diabetic retinopathy (DR) and 22 eyes in 22 patients with branch retinal vascular occlusion (BRVO) showing macular edema were included in this study. The medical records and OCT findings were retrospectively reviewed in patients with SRD-type DME and compared with those with BRVO. The mean number of HF, the mean choroidal thickness, and lipid profiles were analyzed and compared between groups. RESULTS: The mean number of HF was significantly higher in DR group compared to BRVO group. Significant correlation of HF was noted with triglycerides (r = 0.523, P = 0.002). Triglycerides were significantly associated with HF by linear regression (ß = 0.012, 95% CI 0.001-0.024, P = 0.034) and remained significantly associated by multiple linear regression (ß = 0.014, 95% CI 0.003-0.025, P = 0.014). CONCLUSIONS: HF on OCT of DME patients could be indicative of activated microglia. HF are associated with dyslipidemia, especially high triglycerides, suggesting inflammatory reaction from dyslipidemia in diabetic retina.

Topography of the Central Retinal Artery Relevant to Retrobulbar Reperfusion in Filler Complications.

BACKGROUND: Vision loss caused by retrograde occlusion of the central retinal artery is a serious complication of cosmetic filler injections. Salvage methods that involve applying hyaluronidases in the retrobulbar space to degrade filler materials have been proposed recently for rescuing the retinal circulation in an ophthalmic emergency. METHODS: Sixty-six eyeballs and orbital contents were extracted from formalin-embalmed cadavers and dissected carefully to examine the topographic relationship of the central retinal artery and optic nerve. To observe the three-dimensional course of a central retinal artery that invaginates into the optic nerve, serial sections reconstructed at 100-µm intervals using software were visualized in 11 specimens. RESULTS: The central retinal artery ramified from the ophthalmic artery and entered the optic nerve inferiorly at 8.7 ± 1.7 mm (mean ± SD) from the posterior margin of the eyeball. The intraneural course of a central retinal artery changed acutely between the periorbital environment of the fibrous optic nerve sheath, intermediate subarachnoid spaces, and center of the optic nerve stroma. CONCLUSION: When applying a retrobulbar approach for central retinal artery reperfusion with hyaluronidases, the reliable access route is suggested to be at a depth of 3.0 to 3.5 cm from the border of the inferolateral orbital rim, based on consideration of the entry point of the central retinal artery into the optic nerve.

Caseous calcification of the mitral valve annulus: a rare cause of bilateral cerebral and ocular embolisation.

A 65-year-old woman presented with sudden bilateral visual loss of recent onset. She was recently diagnosed with multiple acute stroke syndrome for which she was commenced on antiplatelet therapy. Funduscopic examination revealed bilateral inferotemporal retinal artery occlusions. The recent history of multiple cerebral infarcts combined with the current ocular findings prompted a transoesophageal echocardiogram which successfully revealed caseous calcification of the mitral valve annulus as the source of the numerous sequential emboli, a finding which the conventional transthoracic echocardiogram had failed to disclose as a result of suboptimal image quality. Transoesophageal echocardiography should always be considered as part of the diagnostic workup of retinal arterial occlusive disease, particularly in bilateral lesions, due to its higher yield in identifying posteriorly located cardiac valvular and aortic lesions.

Atypical central retinal artery occlusion as the first presentation of POEMS syndrome: a case report.

BACKGROUND: POEMS syndrome is a plasma cell disorder, which clinically manifests from paraneoplastic syndrome: polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, and skin changes. The most common ocular manifestation is optic disc swelling, whereas other ocular manifestations; cystoid macular edema, serous macular detachment, venous sinus thrombosis, infiltrative orbitopathy, uveitis, neovascularization of the disc, peripapillary choroidal neovascularization and optic disc drusen, had also been reported. CASE PRESENTATION: A 52-year-old Thai man presented with 5-day sudden painless visual loss in the left eye. Ocular examination revealed visual acuity of 20/20 and no light perception in the right and left eye, respectively. Right fundoscopic examination was significant for hyperemic generalized optic disc swelling. Left fundoscopic examination revealed opaque and edematous entire retina giving the appearance of central retinal artery occlusion (CRAO) along with pallid "chalky white" optic disc swelling. Fluorescein angiography showed profound leakage of bilateral optic nerve heads and arteriolar filling defect in macular area along with leakage of small retinal arterioles in the left eye. Indocyanine green angiography demonstrated choroidal filling defect in the left eye only. Neuroimaging showed enhancement and luminal narrowing of left internal carotid artery, early subacute watershed infarctions in the left cerebral hemisphere and pachymeningeal enhancement. Cerebrospinal fluid analysis revealed high protein level with normal opening pressure. Intravenous methylprednisolone was initially started without any benefit. After extensive investigations, diagnosis of "POEMS syndrome" was made based on polyneuropathy, elevated lambda light chain level, elevated plasma vascular endothelial growth factor (VEGF), hepatomegaly, spinal sclerotic bone lesions, and thrombocytosis. Furthermore, sural nerve biopsy demonstrated neuropathy and positive VEGF staining. He was treated with eight cycles of bortezomib, cyclophosphamide and dexamethasone (BorCyDex). Polyneuropathy and thrombocytosis had remarkably improved after 2nd cycle, whereas, visual impairment had shown no recovery. Hepatomegaly was significantly reduced after the completion of BorCyDex. Our case eventually received autologous hematopoietic stem cell transplantation with high dose melphalan. CONCLUSIONS: To our knowledge, we illustrated the first patient given CRAO as the first presentation and ocular finding ever reported in POEMS syndrome. Both cerebral and ocular infarctions were presumably the result of VEGF-induced cranial vasculopathy as evidenced by neuroimaging.

Susac's syndrome: isolated retinal artery occlusion after 10 years of remission / Síndrome de Susac: oclusão isolada da artéria retiniana após 10 anos de remissão

ABSTRACT Susac's syndrome, or microangiopathy of the retina, inner ear, and brain, is a rare condition characterized by the clinical triad of encephalopathy, branch retinal artery occlusion, and sensorineural hearing loss. The complete triad has been documented in 85% of reported cases. At clinical onset, the most common manifestations are central nervous system symptoms, followed by visual symptoms and hearing disturbances. Although the clinical course of Susac's syndrome is usually self-limiting, fluctuating, and monophasic, clinical polycyclic and chronic courses have also been described. Likewise, recurrences of the full triad after more than 10 years of remission have been reported. We describe a 21-year-old woman who presented with branch retinal artery occlusions and magnetic resonance imaging findings compatible with Susac's syndrome without objective hearing loss. After 10 years of remission, the patient complained of visual field loss due to new retinal ischemia. Neither other symptoms nor neuroimaging or audiometry pathologic findings were found during the clinical course.

RESUMO A síndrome de Susac, ou a micro angiopatia da retina, do ouvido interno e do cérebro, é uma condição rara caracterizada pela tríade clínica de encefalopatia, oclusão de ramo da artéria retiniana e perda de audição neuro-sensorial. A tríade completa é documentada em 85% dos casos registrados. No início dos sinais clínicos, a manifestação mais comum relaciona-se ao sistema nervoso central, seguida por sintomas visuais e distúrbios auditivos. Apesar do curso clínico da síndrome de Susac ser usualmente auto limitante, variável e monofásico, cursos clínicos policíclicos e crônicos têm sido também descritos. Do mesmo modo, recorrências da tríade completa após mais de 10 anos de remissão têm sido relatadas. Descrevemos o caso de uma mulher de 21 anos que apresentava oclusões de ramos da artéria retiniana e imagens por ressonância magnética compatíveis com a síndrome de Susac, sem comprometimento objetivo da audição. Dez anos após a remissão, a paciente queixou-se de perda de campo visual devido a uma nova isquemia da retina. Nenhum outro sintoma, ou neuroimagem ou achado audiométrico patológico foi observado durante o curso clínico.

A Review: Proteomics in Retinal Artery Occlusion, Retinal Vein Occlusion, Diabetic Retinopathy and Acquired Macular Disorders.

Retinal artery occlusion (RAO), retinal vein occlusion (RVO), diabetic retinopathy (DR) and age-related macular degeneration (AMD) are frequent ocular diseases with potentially sight-threatening outcomes. In the present review we discuss major findings of proteomic studies of RAO, RVO, DR and AMD, including an overview of ocular proteome changes associated with anti-vascular endothelial growth factor (VEGF) treatments. Despite the severe outcomes of RAO, the proteome of the disease remains largely unstudied. There is also limited knowledge about the proteome of RVO, but proteomic studies suggest that RVO is associated with remodeling of the extracellular matrix and adhesion processes. Proteomic studies of DR have resulted in the identification of potential therapeutic targets such as carbonic anhydrase-I. Proliferative diabetic retinopathy is the most intensively studied stage of DR. Proteomic studies have established VEGF, pigment epithelium-derived factor (PEDF) and complement components as key factors associated with AMD. The aim of this review is to highlight the major milestones in proteomics in RAO, RVO, DR and AMD. Through large-scale protein analyses, proteomics is bringing new important insights into these complex pathological conditions.

Progression of Diabetic Capillary Occlusion: A Model.

An explanatory computational model is developed of the contiguous areas of retinal capillary loss which play a large role in diabetic maculapathy and diabetic retinal neovascularization. Strictly random leukocyte mediated capillary occlusion cannot explain the occurrence of large contiguous areas of retinal ischemia. Therefore occlusion of an individual capillary must increase the probability of occlusion of surrounding capillaries. A retinal perifoveal vascular sector as well as a peripheral retinal capillary network and a deleted hexagonal capillary network are modelled using Compucell3D. The perifoveal modelling produces a pattern of spreading capillary loss with associated macular edema. In the peripheral network, spreading ischemia results from the progressive loss of the ladder capillaries which connect peripheral arterioles and venules. System blood flow was elevated in the macular model before a later reduction in flow in cases with progression of capillary occlusions. Simulations differing only in initial vascular network structures but with identical dynamics for oxygen, growth factors and vascular occlusions, replicate key clinical observations of ischemia and macular edema in the posterior pole and ischemia in the retinal periphery. The simulation results also seem consistent with quantitative data on macular blood flow and qualitative data on venous oxygenation. One computational model applied to distinct capillary networks in different retinal regions yielded results comparable to clinical observations in those regions.

Combined branch retinal vein and artery occlusion in toxoplasmosis / Oclusão combinada de ramo arterial e venoso retinianos em toxoplasmose

ABSTRACT A 22-year-old man complained of low visual acuity and pain in his left eye for five days. His ophthalmological examination revealed 2+ anterior chamber reaction and a white, poorly defined retinal lesion at the proximal portion of the inferotemporal vascular arcade. There were retinal hemorrhages in the inferotemporal region extending to the retinal periphery. In addition, venous dilation, increased tortuosity, and ischemic retinal whitening along the inferotemporal vascular arcade were also observed. A proper systemic work-up was performed, and the patient was diagnosed with ocular toxoplasmosis. He was treated with an anti-toxoplasma medication, and his condition slowly improved. Inferior macular inner and middle retinal atrophy could be observed on optical coherence tomography as a sequela of ischemic injury. To our knowledge, this is the first report of combined retinal branch vein and artery occlusion in toxoplasmosis resulting in a striking and unusual macular appearance.

RESUMO Um paciente do sexo masculino, com 22 anos de idade, queixou-se de redução da acuidade visual no olho esquerdo por 5 dias. O exame oftalmológico mostrou reação de câmara anterior 2+ e uma lesão retiniana esbranquiçada, pouco definida, na porção proximal da arcada vascular temporal inferior. Foram observadas hemorragias retinianas na região temporal inferior estendendo-se à periferia, assim como ingurgitamento venoso, aumento da tortuosidade e palidez isquêmica da retina no mesmo quadrante. Exames laboratoriais corroboraram o diagnóstico de toxoplasmose ocular. O paciente melhorou lentamente após tratamento apropriado. Foi evidenciada atrofia da retina macular inferior interna e média à tomografia de coerência óptica, como sequela da isquemia retiniana. Para nosso conhecimento, este é o primeiro relato de oclusão retiniana combinada de ramo arterial e venoso em toxoplasmose ocular, levando a um aspecto fundoscópico atípico e peculiar.

Retinal Precapillary Arteriolar Occlusion after Coronary Artery Bypass Grafting Surgery.

BACKGROUND: The aim of this study is to evaluate the microembolic changes related to occlusions of precapillary arterioles in the retina during coronary artery bypass grafting (CABG) surgery using fundus photography, and to examine systemic and operational factors related to occurrent lesions. METHODS: Retinal microvascular damage was assessed by color fundus photography one day before CABG surgery, on postoperative day five, and again three months after surgery. In addition to patients' demographics, diabetes mellitus, hypertension, chronic renal failure, and hypercholesterolemia (LDL level) were examined. Smoking history was recorded. Additionally, each patient's carotid Doppler results were ranked by four degrees. Data related to the surgery were recorded. RESULTS: No retinal emboli were seen in any patient before surgery. In fundus photographs taken on the fifth day after surgery, retinal precapillary arteriolar occlusions were seen in 20 (28.57%) of the patients. Lesions were observed to have disappeared in the third month after surgery. There was no significant (P > .05) difference in age, sex, diabetes mellitus, HT ratio, tobacco consumption percentage, LDL values, and Doppler USG distribution between the two groups of patients with and without lesions. However, CABG surgery and cross-clamp removal time measured significantly (P < .05) longer in the group with lesions than in the group without lesions. CONCLUSION: Our results show that retinal microembolism can occur after CABG surgery in association with surgery time and cross-clamp time; however, this does not cause any clinical outcome.

Images in Clinical Medicine. Central Retinal-Vein Occlusion.

A 43-year-old man presented with sudden painless loss of vision in his left eye. Funduscopic examination revealed hyperemia and swelling of the optic nerve, macular edema, diffuse intraretinal hemorrhages, and dilated and tortuous retinal veins.

FDG PET findings of the brain in sudden blindness caused by bilateral central retinal artery occlusion revealing giant cell arteritis.

We report the case of a 73-year-old woman presenting sudden blindness caused by bilateral simultaneous central retinal artery occlusion revealed by ophthalmoscopy. Temporal artery biopsy confirmed the giant cell arteritis. The patient was treated with a systemic steroid without visual recovery. FDG PET/CT was performed 6 months later in the context of persistent inflammatory syndrome. This case shows the close relationship between functional activity and glucose energy metabolism. We observed both bilateral occipital hypometabolism corresponding to loss of functional activity and bilateral temporal (auditory areas) and orbitofrontal hypermetabolism related to compensatory neuronal plasticity.

An anatomic basis for treatment of retinal artery occlusions caused by hyaluronic acid injections: a cadaveric study.

BACKGROUND: In ophthalmic artery occlusion by hyaluronic acid injection, the globe may get worse by direct intravitreal administration of hyaluronidase. Retrograde cannulation of the ophthalmic artery may have the potential for restoration of retinal perfusion and minimizing the risk of phthisis bulbi. The study investigated the feasibility of cannulation of the ophthalmic artery for retrograde injection. METHODS: In 10 right orbits of 10 cadavers, cannulation and ink injection of the supraorbital artery in the supraorbital approach were performed under surgical loupe magnification. In 10 left orbits, the medial upper lid was curvedly incised to retrieve the retroseptal ophthalmic artery for cannulation by a transorbital approach. Procedural times were recorded. Diameters of related arteries were bilaterally measured for comparison. Dissections to verify dye distribution were performed. RESULTS: Cannulation was successfully performed in 100 % and 90 % of the transorbital and the supraorbital approaches, respectively. The transorbital approach was more practical to perform compared with the supraorbital approach due to a trend toward a short procedure time (18.4 ± 3.8 vs. 21.9 ± 5.0 min, p = 0.74). The postseptal ophthalmic artery exhibited a tortious course, easily retrieved and cannulated, with a larger diameter compared to the supraorbital artery (1.25 ± 0.23 vs. 0.84 ± 0.16 mm, p = 0.000). CONCLUSIONS: The transorbital approach is more practical than the supraorbital approach for retrograde cannulation of the ophthalmic artery. This study provides a reliable access route implication for hyaluronidase injection into the ophthalmic artery to salvage central retinal occlusion following hyaluronic acid injection. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266.

High serum thyrotropin levels are associated with retinal arteriolar narrowing in the general population.

BACKGROUND: Recent studies have shown associations of hypothyroidism with arterial blood pressure, atherosclerosis, and inflammation. Based on these pathways, there might also be an association between hypothyroidism and retinal arteriolar narrowing (RAN), a marker of microvascular damage from hypertension, atherosclerosis, and inflammation. Against this background, the aim of this study was to investigate the putative association between serum thyrotropin (TSH) levels and RAN defined by arterio-venous ratio (AVR) from static vessel analysis. METHODS: We used data from 3189 individuals from the second population-based cohort of the Study of Health in Pomerania (SHIP-TREND-0). Thyroid function was defined according to serum TSH and serum diiodothyronine (3,5-T2) levels. Low and high serum TSH levels were defined by the cutoffs 0.3 mIU/L and 3.0 mIU/L. Fundus photography of the central retina was recorded with a nonmydriatic camera, and images were evaluated by one experienced reader. An AVR <0.8 was defined as decreased. Serum TSH levels, low and high TSH, and serum 3,5-T2 levels were associated with AVR by linear regression and with AVR <0.8 by Poisson regression, both adjusted for age, sex, cigarette smoking, alcohol consumption, and intake of beta-blockers. RESULTS: Serum TSH levels were significantly associated with AVR (ß=-0.028 [CI -0.049 to -0.007]; p=0.009) and with a decreased AVR <0.8 (relative risk=2.05 [CI 1.13-3.73]; p=0.019). Individuals with high TSH had a 1.43 higher risk for a decreased AVR ([CI 1.04-1.96]; p=0.027) than individuals with serum TSH levels within the reference range. Serum 3,5-T2 levels were also associated with a decreased AVR (relative risk for an increase of 1 nM=0.45 [CI 0.23-0.87]; p=0.017). CONCLUSIONS: Our results substantiate evidence for an association between hypothyroidism and RAN. Potential mechanisms explaining this association are long-term hypertension, atherosclerotic processes, and inflammation.

A case of Churg-Strauss syndrome and central retinal artery occlusion with good visual recovery.

Here we report a case of Churg-Strauss syndrome (CSS) and central retinal artery occlusion (CRAO), with good visual recovery. A 58-year-old Japanese man with CSS experienced acute painless loss of vision in his right eye. CRAO was diagnosed by fundoscopic findings (retinal whitening with a cherry-red spot). Steroid pulse therapy (methylprednisolone at 1 g daily for 3 days) followed by combined treatment with prednisolone (30 mg/day) and cyclophosphamide (150 mg/day) was administered; his visual acuity recovered to 20/30 in 1 month, and no recurrence has occurred for 1 year. Steroid pulse therapy may be effective for CRAO in CSS patients.

Superselective intraophthalmic artery chemotherapy in a nonhuman primate model: histopathologic findings.

IMPORTANCE: We describe the histopathologic findings in a nonhuman primate (NHP) model of superselective intraophthalmic artery chemotherapy (SSIOAC), detailing ocular and orbital vascular adverse effects. OBJECTIVE: To further document, using comprehensive ocular and orbital histopathology, previously reported toxic effects observed with real-time ophthalmoscopy during SSIOAC in a NHP model. DESIGN: Comparative interventional case series. SETTING: Preclinical trial approved under the guidelines of the Institutional Animal Care and Utilization committee. PARTICIPANTS: Six adult male rhesus macaques (Macacca mulatta). INTERVENTIONS: The right eye of each NHP was treated with 3 cycles of SSIOAC using either melphalan (5 mg/30 mL) or carboplatin (30 mg/30 mL). Both eyes in each animal were enucleated 6 hours after the final procedure, before euthanasia and formalin perfusion of the NHP; we then performed orbital dissection of the arterial vasculature and optic nerves. MAIN OUTCOME MEASURES: Histopathologic examination of the eyes, optic nerves, and orbital vessels of the 6 treated NHPs. RESULTS: We found leukostasis with retinal arteriole occlusion in all treated eyes. Retinal endothelial cells stained positive for 2 inflammatory markers, intercellular adhesion molecule 1 and interleukin 8. Transmission electron microscopy revealed occlusion of the retinal vessels with ultrastructural changes in the endothelial cells and surrounding pericytes. Additional findings included nerve fiber layer infarcts, central retinal artery thrombosis, hypertrophy and occlusion of choroidal arteries with disruption of the internal elastic lamina, patchy choroidal inflammation, and birefringent intravascular foreign bodies. Orbital findings included ophthalmic artery and central retinal artery wall dissection, fracturing of the internal elastic lamina, intimal hyperplasia, and eyelid vessel damage. Optic nerves displayed hemorrhage, leukostasis, and foreign body crystallization. Control eyes, optic nerves, and orbital vessels were normal. CONCLUSIONS AND RELEVANCE: Histopathologic examination of our nonhuman primate model for SSIOAC revealed significant toxic effects in the ocular and orbital vasculature. These findings substantiate previous observations with real-time retinal imaging and parallel reported vascular toxic effects in children with retinoblastoma treated with SSIOAC.