Intraretinal Hemorrhages Research Articles

The astrocyte-expressed integrin αvβ8 governs blood vessel sprouting in the developing retina

The mouse retina is vascularized after birth when angiogenic blood vessels grow and sprout along a pre-formed latticework of astrocytes. How astrocyte-derived cues control patterns of blood vessel growth and sprouting, however, remains enigmatic. Here, we have used molecular genetic strategies in mice to demonstrate that αvβ8 integrin expressed in astrocytes is essential for neovascularization of the developing retina. Selective ablation of αv or β8 integrin gene expression in astrocytes leads to impaired blood vessel sprouting and intraretinal hemorrhage, particularly during formation of the secondary vascular plexus. These pathologies correlate, in part, with diminished αvβ8 integrin-mediated activation of extracellular matrix-bound latent transforming growth factor βs (TGFβs) and defective TGFβ signaling in vascular endothelial cells, but not astrocytes. Collectively, our data demonstrate that αvβ8 integrin is a component of a paracrine signaling axis that links astrocytes to blood vessels and is essential for proper regulation of retinal angiogenesis.

Purtscher-like retinopathy caused by acute pancreatitis

A 30-year-old woman with acute pancreatitis was referred to our eye clinic because of sudden blindness. Visual acuity was reduced to counting fingers in both eyes. Fundoscopy showed cotton-wool spots and intraretinal haemorrhages surrounding a normal optic disc bilaterally (figure A, B). At 3-month follow-up, the patient's retinal findings had much improved spontaneously. However, her visual acuity did not recover completely (right, 20/40, left, 20/25), although the underlying pancreatitis had been treated successfully. Purtscher retinopathy is caused by microembolisation of retinal and choroidal arterioles by fat emboli after severe trauma and is characterised by retinal ischaemia and haemorrhages. Purtscher-like retinopathy shows the same clinical findings but is associated with other diseases, including acute pancreatitis, systemic collagen vascular diseases, chronic renal failure, and thrombotic thrombocytopenic purpura. Enzymes from an inflamed pancreas seem to lead to complement activation, resulting in granulocyte aggregation and subsequent retinal microembolisation. There is no evidence-based treatment for this retinopathy. A 30-year-old woman with acute pancreatitis was referred to our eye clinic because of sudden blindness. Visual acuity was reduced to counting fingers in both eyes. Fundoscopy showed cotton-wool spots and intraretinal haemorrhages surrounding a normal optic disc bilaterally (figure A, B). At 3-month follow-up, the patient's retinal findings had much improved spontaneously. However, her visual acuity did not recover completely (right, 20/40, left, 20/25), although the underlying pancreatitis had been treated successfully. Purtscher retinopathy is caused by microembolisation of retinal and choroidal arterioles by fat emboli after severe trauma and is characterised by retinal ischaemia and haemorrhages. Purtscher-like retinopathy shows the same clinical findings but is associated with other diseases, including acute pancreatitis, systemic collagen vascular diseases, chronic renal failure, and thrombotic thrombocytopenic purpura. Enzymes from an inflamed pancreas seem to lead to complement activation, resulting in granulocyte aggregation and subsequent retinal microembolisation. There is no evidence-based treatment for this retinopathy.

Branch Retinal Vein Occlusion During Fingolimod Treatment in a Patient With Multiple Sclerosis

Fingolimod (FTY720; Novartis) is a new oral drug that acts as a superagonist of the sphingosine-1-phosphate-1 receptor on thymocytes and lymphocytes, sequestering these cells in lymph nodes (1). This medication has been shown to be effective in the management of multiple sclerosis (2,3). The most frequent adverse events reported with fingolimod are nasopharyngitis, influenza, and headache, but cases of arterial vasospasm (4) and reversible cystoid macular edema (5) have also been described. A 47-year-old woman with a 9-year history of multiple sclerosis, who had been treated with fingolimod for the past 6 years, complained of sudden visual loss in her left eye. Visual acuity was 20/20 in the right eye and 20/40 in the left eye. Anterior segment evaluation was unremarkable. The right fundus was normal while a superotemporal branch retinal vein occlusion was noted in the left eye (Fig. 1). Spectral-domain optical coherence tomography (SD-OCT) revealed the presence of intraretinal cystic changes and thickening of the superior nasal macula with foveal involvement (Fig. 2A). The central foveal thickness measured 396 μm. Fluorescein angiography showed the blocking effect of the intraretinal hemorrhages and an area of delayed choroidal filling (Fig. 2B). There was no evidence of retinal vasculitis. Fingolimod was discontinued, and an intravitreal injection of ranibizumab (Lucentis; Novartis) was administered. A thorough evaluation for a coagulation disorder was conducted, but no significant abnormality was detected. The presence of cardiovascular risk factors, such as smoking, arterial hypertension, or diabetes, was also excluded.FIG. 1: Left fundus showing a superotemporal branch retinal vein occlusion.FIG. 2: A. SD-OCT reveals superotemporal macular thickening (top) with intraretinal cystic spaces (bottom). B. Top, fluorescein angiography is consistent with a superotemporal branch retinal vein occlusion and an area of delayed choroidal filling (arrows); bottom, choroid fills late in the angiogram.Three weeks later, vision was 20/20 in the left eye and the SD-OCT showed normalization of the foveal contour without cystic spaces and a mild superonasal macular thickening (Fig. 3).FIG. 3: Three weeks after an intravitreal injection of ranibizumab, there was a near-complete resolution of retinal edema.We are not aware of any previous reports of retinal vein occlusion in patients treated with fingolimod. Although we cannot prove a causal relationship between fingolimod and retinal vein occlusion, we believe that this drug should be considered in the diagnostic algorithm of patients with this retinal vascular disorder. Roberto Gallego-Pinazo, MD Enrique España-Gregori, MD Bonaventura Casanova, MD Diamar Pardo-López, MD Manuel Díaz-Llopis, PhD, MD New University and Polytechnic Hospital La Fe and University of Valencia Valencia, Spain [email protected]

Branch retinal vein occlusion associated with vitreoretinal traction.

Branch retinal vein occlusion (BRVO) is believed to arise at arteriovenous crossing sites. Surgical dissection of the arteriovenous sheath has been proposed as a treatment option, yet induction of a posterior vitreous detachment may be as important in obtaining a successful surgical outcome, suggesting that vitreoretinal traction may play a role in the development of BRVO. A retrospective review of 3 patients presenting with clinical features of BRVO and evidence of vitreoretinal traction at the occlusion site was conducted. All patients presented with mild vitreous hemorrhage. Intraretinal hemorrhages were distributed in an unusual linear pattern along the involved venous segment, suggesting the presence of vitreoretinal traction. Fluorescein angiography demonstrated blocked fluorescence secondary to hemorrhage with delay of venous flow at the avulsion site. Partial avulsion of the involved venous segment was evident on clinical examination, B-scan ultrasound, or optical coherence tomography. Vitreoretinal traction may contribute to the pathogenesis of BRVO in some patients.

Intravitreal voriconazole for the treatment of Aspergillus chorioretinitis

The aim of this article is to report a case of Aspergillus chorioretinitis successfully treated with intravitreal voriconazole based on an interventional case report. An immunodeficient patient, 34 years old, receiving systemic antifungal treatment for 1month for invasive aspergillosis with necrotizing pneumonia and brain metastasis, who presented with blurred vision in his left eye. Visual acuity (VA) was 20/20 in his right eye, and 8/20 in his left eye. Ophthalmological examination showed a paramacular nodular yellowish chorioretinal lesion with intraretinal hemorrhages, in the absence of vitritis or anterior uveitis. The patient was treated with one dose of intravitreal voriconazole (100μg/0.1ml). One week after the intravitreal injection, the patient's VA was 10/20, the retinal lesions had diminished, and the hemorrhages had disappeared. At 3-month follow-up, his AV was 20/20 with a residual retinal scar. The significant and rapid improvement in this patient suggests that early injection of intravitreal voriconazole may be the first therapeutic option in Aspergillus chorioretinitis, obviating the need for vitrectomy.

Peripapillary vitreoretinal traction

Background Vitreoretinal traction syndrome may occur in patients with incomplete posterior vitreous detachment. Although vitreoretinal traction of the macula is well-documented in the literature, the manifestations of peripapillary vitreoretinal traction are rarely discussed. Case report A 62-year-old black woman presented for a comprehensive examination. She reported having uncontrolled diabetes and hypertension. Best-corrected visual acuities were 20/30 in the right eye (OD) and 20/25 in the left eye (OS). Dilated examination found a flame-shaped hemorrhage OD. The optic nerve margins OS were blurred, with the margins appearing elevated with peripapillary intraretinal hemorrhages. Cirrus spectral domain optical coherence tomography (OCT) found the presence of peripapillary vitreoretinal traction with concurrent vitreomacular traction OS. Conclusion Although the effects of vitreoretinal traction are most commonly associated with the macula or peripheral retina, residual attachment can occur at the optic nerve head. Peripapillary vitreoretinal traction can cause optic nerve head elevation with the appearance of edema that must be distinguished from sight- or health-threatening etiologies. OCT is a valuable diagnostic tool in confirming peripapillary vitreoretinal traction.

INTRAVITREAL RANIBIZUMAB FOR MACULAR EDEMA SECONDARY TO CENTRAL RETINAL VEIN OCCLUSION

To evaluate the safety and efficacy of intravitreal ranibizumab for macular edema secondary to central retinal vein occlusion. Patients with macular edema secondary to perfused central retinal vein occlusion were enrolled in this ongoing, prospective, open-label study. Treatment was initiated with monthly intravitreal ranibizumab for 3 months. In the first year, additional injections were administered for edema in quarterly intervals as needed (PRN) for Cohort 1 (n = 10) and monthly PRN for Cohort 2 (n = 10). In the second year of treatments, all patients received monthly PRN treatment. Early Treatment Diabetic Retinopathy Study best-corrected visual acuity, central retinal thickness, fundus photographs, and fluorescein angiograms were evaluated, and the incidence and severity of adverse events were documented. Mean change in best-corrected visual acuity and central retinal thickness improved during the induction phase in both groups. During the remainder of the first year for Cohort 1, initial gains were lost during quarterly treatment but returned with monthly PRN treatment in the second year. For Cohort 2, improvement in best-corrected visual acuity and central retinal thickness from the induction phase was maintained through Month 24. Nineteen of 20 patients experienced a reduction in intraretinal hemorrhage, optic nerve swelling, and/or venous diameter after treatment. One myocardial infarction, one cerebrovascular accident, and no serious ocular adverse events were reported. Iris neovascularization was developed in none of the eyes. Ranibizumab was well tolerated and associated with a greater reduction in macular edema and improvement in visual acuity in the monthly PRN regimen compared with quarterly treatment. Vision lost during the quarterly PRN injection intervals in the first year of Cohort 1 could be regained by switching to monthly PRN dosing.

GEOGRAPHIC ATROPHY IN RETINAL ANGIOMATOUS PROLIFERATION

To describe the occurrence of geographic atrophy in patients with retinal angiomatous proliferation (RAP). Demographics, visual acuity, color fundus photographs, fluorescein and indocyanine green angiograms, and fundus autofluorescence and near-infrared autofluorescence images were reviewed in 53 patients (66 eyes) with RAP. Of 53 treatment-naive eyes, 19 (36%) had atrophy at baseline. Of 66 eyes, 57 (86%) developed de novo atrophy or enlargement of preexisting areas of atrophy during the follow-up (median, 17 months; range, 3-53 months) after treatment. Areas of atrophy were observed at the site of the RAP (58 of 66 eyes, 88%) of a previously existing pigment epithelial detachment (18 of 44 eyes; 41%) and elsewhere (43 of 66 eyes, 65%). At presentation, RAP was found to be frequently associated with increased autofluorescence at the fovea because of cystoid macular edema (36 of 53 eyes, 68%) and reduced autofluorescence because of hard exudation (38 of 53 eyes, 72%) and intraretinal hemorrhages (32 of 53 eyes, 60%). Background reticular (39%) and homogeneous (36%) autofluorescence were most commonly observed. Geographic atrophy occurs frequently in patients with RAP after treatment. This information, if confirmed in other cohorts, would be valuable for the counseling of patients with this disease and for the understanding of the pathogenesis of this condition and its progression after treatment.

Follow-up of lupus choroidopathy with optical coherence tomography

A 36-year-old female followed with the diagnosis of systemic lupus erythematosus complained of bilateral visual loss. Ophthalmological examination revealed disc edema with irregular borders, edematous and pale retina with widespread cotton wool spots, intraretinal hemorrhages and serous retinal detachment in both eyes. Optical coherence tomography (OCT) scans showed intraretinal and subretinal fluid creating cystic cavities with central subfield macular thickness values of 994 and 912( )µm in the right and left eye, respectively. The follow-up scans after the treatment with systemic steroid, acetylsalicylic acid and cyclosporine documented resolution of this fluid accumulation and a decrease in macular thickness measurements. These clearly demonstrated that OCT, which is a fast, objective and non-invasive technology, may be an adjunctive imaging tool for the diagnosis and follow-up of lupus choroidopathy.

Diabetic Papillopathy: Current and New Treatment Options

Diabetes mellitus is a growing global epidemic. Patients with this disease present with a variety of health conditions, including a number of ocular complications that threaten vision, such as proliferative diabetic retinopathy and macular edema. Diabetic papillopathy, another potential ocular complication from diabetes, is a self-limiting, sometimes bilateral disease that may affect both type 1 and type 2 diabetics. It is characterized by optic disc swelling caused by vascular leakage and axonal edema in and around the optic nerve head. Occasionally, it may be accompanied by intraretinal hemorrhages and hard exudates. Diabetic papillopathy tends to be mild and is usually associated with good visual prognosis; however, there are some cases in which permanent visual impairment can develop. The pathogenesis remains largely unknown, but there has been evidence suggestive of its associations with a small cup/disc ratio and rapid reduction in glycemia. There is no validated therapy for diabetic papillopathy; however, current case reports have shown promising results after local injections of corticosteroids as well as bevacizumab (Avastin), a potent monoclonal antibody that has been employed for the treatment of ocular vaso-proliferative diseases such as choroidal neovascular membranes associated with age-related macular degeneration and proliferative diabetic retinopathy.

Preliminary clinical analysis of neovascular glaucoma secondary to carotid artery disease

Background: Neovascular glaucoma (NVG) is a rare but severe complication of hypoperfusion retinopathy. Our objective was to analyse the clinical features of NVG secondary to carotid artery atherosclerosis, moyamoya disease and Takayasu arteritis.Methods: Thirty‐six cases (36 eyes) with hypoperfusion retinopathy associated with NVG were retrospectively analysed. Each patient had their visual acuity assessed and fundus examined by fundus fluorescein angiography, colour Doppler flow imaging, magnetic resonance angiography, digital subtraction angiography and other techniques.Results: Eyes belonging to 30 males and six females were analysed. There were 24 right eyes and 12 left eyes. The ages of these patients ranged 18 to 78 years and the mean age was 40 years. The visual acuities ranged from light perception to 0.8 (decimal notation). Posterior segment manifestations included mid‐peripheral intraretinal haemorrhages and narrowed retinal arteries. All eyes were associated with either an ipsilateral common carotid artery obstruction or a severe bilateral obstruction of the internal carotid arteries.Conclusions: The characteristic clinical features are presented during the process of the disease. Degeneration of the ocular fundus was predominantly on one side. The retinal manifestations included mid‐peripheral haemorrhages and dilated retinal veins. High intraocular pressure and excavation and atrophy of the optic disc were common. In the eyes that were examined, neovascularisation was observed in the iris and anterior chamber and various visual field defects were present.

Intravitreal Anti-VEGF Bevacizumab (Avastin) for External Beam-Related Radiation Retinopathy

To report on intravitreal bevacizumab treatment for external beam radiation therapy (EBRT)-related radiation maculopathy. Three patients (4 eyes) with EBRT-related maculopathy were treated with periodic (4- to 8-week) intravitreal injections of bevacizumab (1.25 mg in 0.05 cc). Outcome measures included best-corrected Early Treatment Diabetic Retinopathy Study visual acuity, retinal examination, fundus photography, fluorescein angiography, and optical coherence tomography. Patients were diagnosed with Stage 3 radiation maculopathy occurring 12, 19, and 48 months after irradiation. One received 50 Gy of 6-MV photon EBRT for a maxillary carcinoma, the second 30.6 Gy of 6-MV photon EBRT for intraocular lymphoma, and the third 72 Gy proton beam irradiation for adenoid cystic carcinoma of the lacrimal gland. With up to 33 months follow-up, visual acuities improved (8 and 11 letters) in 2 eyes, gained 5 letters in 1 eye and 1 decreased 5 letters from 20/16 to 20/20. All cases demonstrated clinical findings of decreased intraretinal hemorrhages, cotton-wool spots, and retinal edema. There were no significant ocular or systemic side effects. Intravitreal anti-VEGF therapy was associated with reductions of EBRT-related retinopathy. No ocular or systemic side effects were noted. Anti-VEGF therapy may be considered radiation maculopathy secondary to EBRT.

Beidseitiges akutes Engwinkelglaukom im Rahmen einer Hantavirus-Infektion

A poor general condition of patients with hemorrhagic fever and elevated creatinine should raise suspicion of a systemic infection with Hantavirus. This can often also cause ocular changes. Above all, changes of intraocular pressure, in our case bilateral acute angle-closure glaucoma, due to edema and hemorrhage in the ciliary body result in anterolateral rotation of the iris-lens diaphragm with closure of the chamber angle. It can also cause a transient myopia, and intraretinal hemorrhages can also occur. Hantavirus infection is mostly transmitted through red-backed voles in Europe. The predominant type in Europe is the Puumala virus that can lead to an epidemic nephropathy with high fever, headache, gastrointestinal complaints, and an impaired renal function to the point of renal failure. No specific treatment is needed, but adequate symptomatic therapy is of utmost importance. When the infection has been overcome, complete recovery is possible. Measures for prophylaxis should be taken with respect to contact with mice and their excreta.

Effects of intravitreal anti-vascular endothelial growth factor treatment on retinal vasculature in retinal vein occlusion as determined by ultra wide-field fluorescein angiography.

To investigate both peripheral and central retinal vascular changes after intravitreal anti-vascular endothelial growth factor (VEGF) therapy in the setting of acute retinal vein occlusion (RVO). Two patients with macular edema, one secondary to central RVO (CRVO) and one secondary to branch RVO (BRVO), underwent ultra wide-field (200°) photography and fluorescein angiography before and after a single intravitreal injection of an anti-VEGF agent. The patient with CRVO received an intravitreal injection of ranibizumab (0.5 mg/0.05 mL). The patient with BRVO received an intravitreal injection of bevacizumab (1.25 mg/0.05 mL). The eye with CRVO was reevaluated with ultra wide-field photography and fluorescein angiography at 7 days and 35 days after treatment. The eye with BRVO was reevaluated with ultra wide-field photography and fluorescein angiography at 30 days after treatment. Photographs and fluorescein angiographic results were analyzed for posttreatment changes in arteriovenous transit time, vessel caliber, vessel leakage, peripheral capillary nonperfusion, retinal hemorrhages, and nerve fiber layer infarcts. In both eyes, there were no changes detected in the arteriovenous transit time or peripheral capillary nonperfusion after anti-VEGF therapy. A reduction in intraretinal hemorrhages and nerve fiber layer infarcts was observed at 7 days and 35 days after treatment in the patient with CRVO and at 30 days after treatment in the patient with BRVO. A decrease in vessel caliber was observed at 7 days after treatment in the patient with CRVO and at 30 days after treatment in the patient with BRVO. In the patient with CRVO, an increase in vessel caliber with a recurrence of vascular leakage was noted at the visit on Day 35. Anti-VEGF therapy in the setting of RVO may initially decrease vessel caliber, retinal hemorrhages, and nerve fiber layer infarcts but does not appear to affect arteriovenous transit time or areas of peripheral capillary nonperfusion after a single treatment. The beneficial effects of anti-VEGF therapy in RVO appear transient, and multiple injections may be required for control of macular edema. Ultra wide-field angiography can be a useful tool in monitoring the treatment of RVO.

Exudative retinal detachment and angle closure glaucoma as the presenting signs of primary pulmonary hypertension.

Primary pulmonary arterial hypertension is a rare systemic condition that may present with distinct ocular findings. To report a patient whose ophthalmic manifestations led to a diagnosis of pulmonary arterial hypertension. A 58-year-old woman presented with bilateral serous detachments, angle closure, dilated episcleral blood vessels, subretinal drusenoid-like deposits, and intraretinal hemorrhages. She was diagnosed with pulmonary arterial hypertension. Her ocular findings resolved once her underlying systemic disorder had been treated. To our knowledge, this is the first reported case in which an ophthalmic evaluation led to the diagnosis of pulmonary arterial hypertension.

Catastrophic antiphospholipid antibody syndrome and cocaine abuse associated with bilateral retinal vascular occlusions.

To describe a case of bilateral central retinal vein occlusion and central retinal artery occlusion associated with antiphospholipid antibody syndrome and cocaine abuse. A single case report of a 44-year-old woman with a history of cocaine abuse, vasculitis, and 3 spontaneous abortions who developed painless complete loss of vision in both eyes concurrently with progressive motor and sensory polyneuropathy. The patient underwent an extensive laboratory, radiographic, ophthalmologic, and pathologic workup. Diagnosis of catastrophic antiphospholipid antibody syndrome was made based on established clinical and laboratory criteria, including a positive Russell's viper venom test, history of three spontaneous abortions and evidence of microvascular and macrovascular venous occlusions, and multiorgan failure. Urine toxicology screen was positive for cocaine metabolites. Her clinical course was remarkable for progressive mononeuritis multiplex and quadriplegia. She had no light perception on presentation, and fundus examination revealed extensive preretinal, intraretinal, and subretinal hemorrhages. Fluorescein angiography revealed complete occlusion of central retinal arteriolar and venular flow and retinal hemorrhages in both eyes. Bilateral central retinal vein occlusion and central retinal artery occlusion have been rarely reported in the literature and are often associated with underlying thrombotic risk factors, such as antiphospholipid antibody syndrome. Workup for underlying hypercoagulability and/or cocaine use should be considered in atypical and bilateral cases of central vein or artery occlusion. In this case, bilateral central retinal artery and vein occlusions developed as manifestations of catastrophic antiphospholipid antibody syndrome, which has not been previously reported.

Decompression Retinopathy after ExPRESS Shunt Implantation for Steroid-Induced Ocular Hypertension: A Case Report

Purpose. To present a unique case of decompression retinopathy after the implantation of ExPRESS drainage device. Method. A 25-year-old female patient underwent implantation of ExPRESS drainage device in the left eye for the management of steroid-induced ocular hypertension. Results. On the postoperative day one, best-corrected visual acuity in the left eye was 20/50. Fundus examination revealed diffuse intraretinal hemorrhages, some white-centered, throughout the retina. There was also marked tortuosity to the retinal vasculature and no evidence of choroidal effusion. Intravenous fluorescein angiography and indocyanine green did not contribute to the aetiopathogenesis. Conclusion. Decompression retinopathy can occur following the implantation of ExPRESS drainage device. It is very important to be aware of this complication in patients with relatively high intraocular pressure who is planned for filtration surgery, including the ExPRESS implant.

Supraselective intra-arterial chemotherapy: evaluation of treatment-related complications in advanced retinoblastoma

Purpose:The purpose of this study is to report the complication profile and safety evaluation of supraselective intra-arterial melphalan chemotherapy in children undergoing treatment with advanced retinoblastoma.Methods:Twelve eyes of 10 children with advanced retinoblastoma (Reese-Ellsworth Group Vb or International Classification Group D) were treated with supraselective intra-ophthalmic artery infusion of melphalan. Eleven eyes of nine children had previously failed traditional management with systemic chemotherapy and laser ablation and underwent intra-ophthalmic artery infusion of melphalan as an alternative to enucleation. Serial ophthalmic examinations, retinal photography, and ultrasonographic imaging were used to evaluate treatment regime.Results:Ophthalmic artery cannulation was successfully performed in 12 eyes of 10 patients (total 16 times). Striking regression of tumor, subretinal and vitreous seeds were seen early in each case. No severe systemic side effects occurred. Grade III neutropenia was seen in one patient. No transfusions were required. Three patients developed a vitreous hemorrhage obscuring tumor visualization. One patient developed periocular edema associated with inferior rectus muscle inflammation per orbital MRI. This same patient had scattered intraretinal hemorrhages and peripapillary cotton wool spots consistent with a Purtscher’s-like retinopathy that resolved spontaneously. At the 6-month follow-up examination, nine eyes had no evidence of tumor progression, whereas three eyes were enucleated for tumor progression. In each enucleated case, viable tumor was identified on histopathologic examination.Conclusions:Ophthalmic intra-arterial infusion with melphalan is an excellent globe-conserving treatment option in advanced retinoblastoma cases with minimal systemic side effects. Local toxicities include microemboli to the retina and choroid (1/12, 8%), vitreous hemorrhage (3/12, 25%), and myositis (1/12, 8%). Enucleation remained a definitive treatment for tumor progression in 3 of 12 eyes in this small case series with limited follow-up. Further studies are necessary to establish the role of supraselective intra-arterial melphalan chemotherapy for children with retinoblastoma.

Fenretinide-Associated Multilayered Retinal Hemorrhage in a Patient with Hairy Cell Leukemia

Intravenous fenretinide (4-HPR), a cytotoxic retinoid, is being evaluated as part of a phase I clinical trial for patients with hematologic malignancies. In its orally administered form, it is also being evaluated for the treatment of various malignancies and geographic atrophy in subjects with the dry form of age-related macular degeneration. The authors report a case of acute large subretinal and intraretinal hemorrhage noted immediately after initiation of intravenous fenretinide therapy in a patient with hairy cell leukemia. This case highlights the importance of considering multilayered retinal hemorrhage as a possible side effect of fenretinide therapy, especially in patients with underlying hematologic abnormalities.

Ocular Findings in a Patient with Castleman’s Disease Before and After Treatment with Immunosuppression and Plasmapheresis

A 12-year-old girl with a 3-month history of epistaxis and Castleman's disease presented with blurred vision in both eyes for 2 weeks. Indirect ophthalmoscopy revealed a blurred optic disc margin, venous engorgement and tortuosity, intraretinal hemorrhages and cotton wool spots, and serous detachment of the neurosensory retina in the posterior pole of each eye. Fluorescein angiography and laboratory tests revealed abnormalities consistent with the clinical examination. Six months following institution of immunosuppressive treatment, cryoglobulin levels decreased and visual acuity and funduscopic abnormalities were markedly improved. However, a few microaneurysms, retinal hemorrhages, and venous engorgement and tortuosity persisted. One month after the cessation of immunosuppressive treatment, symptoms related to the hyperviscosity syndrome recurred and the patient was treated with one session of plasmapheresis. One month after the plasmapheresis, the patient's symptoms resolved, laboratory values were normal, visual acuity was 20/15 in both eyes, and the funduscopic examination of each eye was unremarkable.