Clinical Features of Central Retinal Vein Occlusion With Inflammatory Etiology

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1 ORIGINAL STUDY Clinical Features of Central Retinal Vein Occlusion With Inflammatory Etiology Chikako Yoshizawa, MD,* Wataru Saito, MD, PhD,*Þ Manabu Kase, MD, PhD,þ and Susumu Ishida, MD, PhD*Þ Purpose: The purpose of this study was to characterize central retinal vein occlusion (CRVO) with inflammatory etiology. Design: A retrospective study. Methods: We retrospectively reviewed 51 eyes of 48 patients with CRVO between 2004 and 2009 and investigated whether they had inflammatory findings related to retinal vasculitis, that is, severe peripheral retinal vascular changes based on fluorescein angiography and anterior vitreous cells. The extent of vascular leakage was classified as mild, moderate, and severe in angiographic images. Results: Six eyes of 5 patients (11.8%) had both inflammatory criteria. All patients were male and with a diagnosis of ischemic CRVO. No causative etiology was detected in any patient. The mean age was 46.4 (SD, 23.3) years. The age range was not limited to young generation. These patients received systemic corticosteroid therapy with a mean follow-up period of 41.8 months. The mean logmar visual acuity [1.29 (SD, 0.77)] and central retinal thickness [ (SD, 399.0) Km)] at the initial visit were significantly (P = and P = 0.001) improved at the final visit [0.94 (SD, 0.69) and (SD, 135.4) Km, respectively]. Conclusions: Central retinal vein occlusion with idiopathic inflammatory conditions appears to have clinical characteristics of broad age range and good response to systemic corticosteroid therapy. Key Words: central retinal vein occlusion, retinal vasculitis, inflammation, systemic corticosteroid therapy, anterior vitreous cells (Asia-Pac J Ophthalmol 2012;1: 270Y276) Central retinal vein occlusion (CRVO) is a nonspecific condition that results from obliteration of the central retinal vein, often in the prelaminar region of the optic disc, and presents with uniform flame-shaped pandirectional retinal hemorrhages that are fewer in number toward the periphery of the retina. Fluorescein angiography (FA) is usually necessary to examine the extent of retinal ischemia in CRVO. In elderly CRVO patients, staining of vascular walls in FA can also be observed mildly at the large retinal veins but not at the peripheral retinal veins. 1 This staining is similar to the distribution of retinal hemorrhages in CRVO. The pathogenesis of CRVO is multifactorial. As risk factors for CRVO, cardiovascular diseases, rheological abnormalities, thrombophilia, and blood hyperviscosity have been reported. 2 However, the precise mechanisms in this pathology remain unclear. Clinically, to classify the pathogenesis, it is customary to distinguish CRVO by the age of onset. 3,4 Central retinal vein From the Departments of *Ophthalmology, and Ocular Circulation and Metabolism, Hokkaido University Graduate School of Medicine; and Department of Ophthalmology, Teine Keijinkai Hospital, Sapporo, Japan. Received for publication April 28, 2012; accepted June 27, The authors have no funding or conflicts of interest to declare. Reprints: Chikako Yoshizawa, MD, Department of Ophthalmology, Hokkaido University Graduate School of Medicine, N-15, W-7, Kita-ku, Sapporo , Japan. cyoshiza@med.hokudai.ac.jp. Copyright * 2012 by Asia Pacific Academy of Ophthalmology ISSN: DOI: /APO.0b013e318266de04 occlusion frequently occurs in patients beyond the fifth decade of life who have arteriosclerotic background. 4 The condition is much less common among young adults younger than 40 years. 2,5,6 Inflammatory mechanisms are generally suggested in younger patients, and the disease is often called CRVO in young adults or papillophlebitis. 3,7 These patients can have involvement of anterior vitreous cells and retinal vascular sheathing and/or wall staining with leakage in FA in the peripheral region. 8,9 Visual acuity in most young patients with CRVO recovers to better than 20/40, but about one-fifth of young patients have poor visual outcomes due to development of severe retinal ischemia and neovascular formation. 3,6,7 Suggested contributing causes for CRVO in young adults include arteriosclerotic diseases (despite the younger age) and hypercoagulability (hyperviscosity or platelet abnormality), 3,7 as well as inflammatory etiology. Elderly CRVO patients may also be affected by an inflammatory or autoimmune mechanism; however, such an inflammatory condition is not generally recognized. Distinguishing the pathogenesis of CRVO based on age alone may thus be problematic. Retinal vasculitis occurs either as an isolated idiopathic condition or in association with infectious or systemic inflammatory diseases. 10 Active retinal vasculitis has ophthalmic findings of retinal vascular sheathing and anterior vitreous cells. 10 Fluorescein angiography can sensitively confirm the inflammatory signs, which are demonstrated by staining of retinal vessel walls and leakage from the vessels. When the activity of retinal vasculitis is severe, peripheral retinal vessels may be damaged. Together with occlusion of the surrounding retinal capillaries, these findings are called occlusive retinal vasculitis. 11 Clinical features and diagnostic criteria of CRVO associated with retinal vasculitis, especially in older patients, remain unresolved. We herein report clinical features of CRVO patients with idiopathic inflammatory etiology over broad age range. MATERIALS AND METHODS Chart Review of CRVO Patients The medical records, fundus photographs, and FA images (Topcon TRC-50IA, Topcon, Tokyo, Japan; Kowa VX-10, Kowa, Nagoya, Japan) of 51 eyes of 48 patients (female n = 23, male n = 25) with a diagnosis of CRVO at the ophthalmology clinic of Hokkaido University Hospital from January 2004 to December 2009 were reviewed retrospectively, after approval from the institutional review board. The patients ages ranged from 16 to 85 years [mean age, 60.1 (SD, 15.8) years]. The records were carefully examined whether the patients had findings of vasculitis. We defined the parameters of vasculitis as the following 2 criteria: (1) severe retinal vascular leakage in the peripheral region based on FA images and (2) presence of anterior vitreous cells. All of the patients who had both of the inflammatory findings were administered high-dose systemic corticosteroid therapy. We followed the clinical course of these patients. This study adhered to the tenets of the Declaration of Helsinki Asia-Pac J Ophthalmol & Volume 1, Number 5, September/October 2012

2 Asia-Pacific Journal of Ophthalmology & Volume 1, Number 5, September/October 2012 CRVO With Inflammatory Etiology Criteria for CRVO With Inflammatory Etiology To quantify the extent of retinal vascular staining with leakage in the peripheral region, the findings were classified as mild, moderate, and severe (Figs. 1AYC) by confirming FA images at approximately 6 minutes after the intravenous injection of fluorescein sodium at the initial visit. Regarding the sites for evaluation, retinal vessels located more peripherally than the second branch of the trunk vessels were selected. Mild type is defined as having little leakage. Severe type is defined as having strong vascular staining and leakage that makes retinal vessel contours obscure [Fig. 1C (arrows)]. Moderate type is defined as being intermediate between mild and severe types. Two ophthalmologists (C.Y. and W.S.) independently classified the retinal peripheral findings of all the 51 cases in a masked fashion, and the rate of concordance was calculated. The extent of inflammatory cells (leukocytes) in the anterior vitreous [Fig. 1D (arrows)] was classified according to the standard grading for anterior chamber cells 12 ; namely, the number of cells in a field size of 1 1 mm slit-lamp beam is less than 1 cell for grade 0, 1 to 5 cell(s) for grade 0.5+, 6 to 15 cells for grade 1+, 16 to 25 cells for grade 2+, 26 to 50 cells for grade 3+, and greater than 50 cells for grade 4+. Eyes with preretinal and/or vitreous hemorrhage were excluded to clearly determine the severity of peripheral retinal findings and to rule out erythrocytes derived from newly formed vessels to accurately distinguish leukocytes. Ophthalmic Examinations Before systemic corticosteroid therapy, the patients who had both inflammatory conditions underwent ophthalmic examinations including decimal best-corrected visual acuity (VA), visual field testing with Goldmann perimetry, indirect ophthalmoscopy, FA, and optical coherence tomography (OCT). Central retinal thickness (CRT) in OCT (OCT Ophthalmoscope C7; Nidek, Gamagori, Japan) was determined by measuring the distance between the inner limiting membrane and the retinal pigment epithelium (RPE) at the macula. During the follow-up period, VA and CRT were measured at each visit. Fluorescein FIGURE 1. Criteria for CRVO with inflammatory etiology. Photographs showing peripheral retinal vascular leakage (AYC) and anterior vitreous cells (D) in patients with CRVO. AYC, The extent of vascular wall staining and dye leakage at the midperipheral to peripheral region. D, Infiltrating cells in the anterior vitreous. TABLE 1. Peripheral Retinal Vascular Leakage and Anterior Vitreous Cells in Patients With CRVO Peripheral Retinal Vascular Leakage No. Eyes (%) Anterior Vitreous Cells (+) (j) Age Mean (SD), Range, y Mild 30 (58.8) (13.8), 27Y85 Moderate 15 (29.4) (14.8), 36Y79 Severe 6 (11.8) (23.3), 16Y68 Total (15.8), 16Y85 angiography was performed before and after treatments. Statistical analyses of mean CRT and VA were performed using paired t test before and after treatment, and differences were considered statistically significant at P G Systemic Examinations Full blood counts, erythrocyte sedimentation rate, serum lipids, serum and urine glucose, hemoglobin A 1c, endogenous coagulation function, protein C, angiotensin-converting enzyme, serum antinuclear antibody, rheumatoid factor, antineutrophil cytoplasmic antibodies, and antiphospholipid antibody together with electrocardiography were examined. Serologic tests and antibody titers for toxoplasmosis, syphilis, Bartonella henselae, herpes simplex virus, varicella zoster virus, and Epstein-Barr virus were examined to exclude the possibility of infectious diseases. Chest radiography and QuantiFERON were examined to rule out tuberculosis. In some patients with young onset (patients 1 and 3) or bilateral development (patient 5), brain and orbital magnetic resonance imaging was performed to rule out intracranial and optic nerve diseases. RESULTS Classification of CRVO Based on Inflammatory Findings Table 1 shows patient distribution depending on the 2 inflammatory criteria of peripheral retinal vascular leakage and anterior vitreous cells in all the CRVO patients. Regarding the severity of vascular leakage, mild, moderate, and severe types were observed in 30, 15, and 6 eyes, respectively. The rates of concordance of the 2 ophthalmologists for mild, moderate, and severe types were 96%, 92%, and 100%, respectively. All eyes with severe type exhibited ischemic CRVO. Anterior vitreous cells were involved in none of the eyes with mild type, and only 1 eye with moderate type. All 6 eyes of 5 patients with the severe vascular pattern had also apparent anterior vitreous cells. The frequency of patients with both severe vascular leakage and anterior vitreous cells was 11.8% of all eyes with CRVO. The age range of patients with severe type was broad and not limited to young generation, although the group with the severe type was significantly younger than the group with the mild type (Student t test, P = 0.02). There were no significant (P = 0.18, P = 0.23) differences between moderate and severe or between mild and moderate. Clinical Characteristics of Patients With Inflammatory CRVO The clinical characteristics of the 6 eyes of 5 patients with inflammatory CRVO are summarized in Table 2. All patients were male. The mean age at the initial visit was 46.4 years (range, 16Y68 years). Notably, older than 55 years were 3 of the * 2012 Asia Pacific Academy of Ophthalmology 271

3 Yoshizawa et al Asia-Pacific Journal of Ophthalmology & Volume 1, Number 5, September/October 2012 TABLE 2. Clinical Characteristics of Patients With CRVO With Inflammatory Conditions Treatments/Duration of Corticosteroid Therapy, mo Visual Acuity CRT, Km Ocular Complications Vascular Staining NPA Anterior Vitreous Cells Visual Field Defect Initial Final Initial Final Follow-Up, mo Unilateral/ Bilateral Age, y/ Sex No. 1 16/M Unilateral BSE + CS VH Pulse, PC, PPV/ /M Unilateral CS Oral PSL, STTA, IVB, PC/ /M Unilateral Nasal island NVG,VH Pulse, IVB, PC, PPV, TLE/7 4 68/M Unilateral CS Oral PSL, STTA, IVB, PC/ /M Bilateral (R) Nasal island NVG Pulse, STTA, IVB, PC/22 Bilateral (L) BSE + CS Pulse, STTA, PC/22 M indicates male; R, right; L, left; BSE, blind-spot enlargement; CS, central scotoma; NPA, retinal nonperfusion area; VH, vitreous hemorrhage; NVG, neovascular glaucoma; Pulse, methylprednisolone pulse therapy; PC, retinal photocoagulation; PPV, pars plana vitrectomy; TLE, trabeculectomy. 5 patients, although the mean age of this group proved to be lower because of inclusion of 2 young patients. The mean duration of clinical follow-up was 41.8 (SD, 14.1) months (range, 31Y66 months). The mean duration of symptom before the initial visit was 3.2 (SD, 2.8) months (range, 1Y8 months). Bestcorrected VA at the initial visit was Q0.5 in 1 eye, 0.1Y0.5 in 1 eye, and G0.1 in 4 eyes. Best-corrected VA at the final visit was 0.5 or greater in 1 eye, 0.1 to 0.5 in 3 eyes, and less than 0.1 in 2 eyes. Compared with the initial visit [1.29 (SD, 0.77)], the average logmar VA was significantly (paired t test, P =0.004) improved at the final visit [0.94 (SD, 0.69)]. Goldmann perimetry showed blind-spot enlargement in 2 eyes, central scotoma in 4 eyes, and a nasal island in 2 eyes. Four patients were Japanese, and 1 was Chilean (patient 3). Ophthalmic Findings in Patients With Inflammatory CRVO Funduscopically, all the 6 eyes with inflammatory CRVO exhibited retinal hemorrhages, swollen optic discs, retinal venous engorgement and tortuosity, and macular edema and/or serous retinal detachment (SRD). In addition, retinal vascular sheathing was apparently seen in 2 eyes [Figs. 2C and 4B (arrows)]. Lipid deposition from the peripapillary to the midperipheral region was seen in 3 eyes (Figs. 2C, G, and 4B). In FA, dilated retinal capillaries within the optic disc and around the peripapillary area were observed in 3 eyes [Figs. 2D and 3A (arrows)], suggesting marked obstruction of the central retinal vein. Approximately 6 minutes after dye injection, strong retinal vascular wall staining and/or leakage extended diffusely from the large retinal veins at the posterior pole to the periphery [Figs. 2B, D, F, and H (arrows) and 4C, D (arrows)]. Retinal capillaries surrounding the inflamed retinal veins were occluded at more than 2 quadrants (Figs. 2B, D, F, and H; 3A and B; and 4C). During follow-up, vitreous hemorrhage occurred in 2 eyes (patients 1 and 3) and was successfully removed by pars plana vitrectomy. Effect of Systemic Corticosteroid Treatment on VA and CRT in Inflammatory CRVO Treatments consisted mainly of methylprednisolone pulse therapy (1000 mg/d) followed by oral corticosteroid therapy in 3 patients and oral corticosteroid therapy tapered from prednisolone (PSL) 30 mg/d in 2 patients. The mean duration of systemic corticosteroid therapy was 14.1 (SD, 5.5) months (range, 7Y22 months). As additional treatments before or at initiation of systemic corticosteroid therapy, 5 of 6 eyes except patient 1 also received sub-tenon triamcinolone acetonide (STTA) and/ or intravitreal bevacizumab (IVB) injections. All the 5 eyes had recurrence of macular edema following these injections; however, the edema was absorbed with continuation of systemic corticosteroid therapy for several months. Panretinal photocoagulation was performed in all 6 eyes for occluded retinal capillaries, as described previously. 13 In contrast, no patient received grid macular laser photocoagulation. After systemic corticosteroid treatment, the extent of the vascular leakage in FA resolved in all eyes. The mean logmar VA (Fig. 5A) at the initial visit [1.29 (SD, 0.77)] was significantly (paired t test, P = 0.004) improved at the final visit [0.94 (SD, 0.69)]. In OCT, the mean CRT (Fig. 5B) reduced significantly (paired t test, P = 0.001) from (SD, 399.0) Km before treatment to (SD, 135.4) Km at the final visit. The moderate excess of the final CRT over its reference range could be attributed to patients 3 and 5 (L), as shown in Table 2. The persistent macular edema in patient 3 may result possibly from RPE pump dysfunction due to his delay of the initial visit after onset, which was * 2012 Asia Pacific Academy of Ophthalmology

4 Asia-Pacific Journal of Ophthalmology & Volume 1, Number 5, September/October 2012 CRVO With Inflammatory Etiology FIGURE 2. Fundus and FA findings in eyes with inflammatory CRVO. Fundus (A, C, E, G) and FA (B, D, F, H) findings in patients 2 (A, B), 3 (C, D), 4 (E, F), and 5 (G, H) with CRVO with inflammatory conditions. Strong retinal vascular wall staining and/or leakage extended diffusely from the large retinal veins at the posterior pole to the periphery (arrows in B, D, F, H). approximately 8 months, indeed long enough to develop neovascular glaucoma. In patient 5 (L), IVB injection was a candidate option for additional treatment, but his well-preserved best-corrected VA of 1.2 precluded our further intervention. In a 63-year-old patient with ischemic maculopathy (patient 5), the areas of dilated and stagnant retinal capillaries within posterior pole lessened 4 days after corticosteroid pulse therapy (arrows in Figs. 3A, B), suggesting that the central retinal vein was reperfused. Visual acuity also improved from 0.01 to 0.07 with rapid disappearance of macular edema (Figs. 3C, D). Systemic Findings in Patients With Inflammatory CRVO Based on medical history, all the 5 patients were systemically healthy except for well-controlled hypertension in 2 patients (patients 4 and 5). None of the patients exhibited clinical symptoms before the onset of visual complaints such as lymph node swelling, fever, or chronic cough. Systemic screening revealed no abnormalities in any patient. Case Presentation: A Young Patient With Severe Inflammatory Findings A healthy 16-year-old male adolescent (patient 1) presented with central visual loss in the left eye. His VA was 1.5 (OD) and 0.04 (OS). Slit-lamp examination revealed moderate anterior vitreous cells (OS). Funduscopic examination showed CRVO with macular edema and SRD (OS). Oral PSL was immediately initiated from 30 mg/d and gradually tapered. Macular edema and SRD reduced within 1 week, and VA improved to 1.0 by 4 weeks after treatment (Fig. 4A). However, his left VA FIGURE 3. Prompt reperfusion of capillaries and reduction of macular edema in response to systemic corticosteroid therapy in an elderly case of inflammatory CRVO. Fluorescein angiography (A, B) and OCT (C, D) findings in a 63-year-old man (patient 5). Four days after pulse therapy, retinal capillary dilatation (arrows in A) rapidly improved (arrows in B) in parallel with disappearance of macular edema (C, D). * 2012 Asia Pacific Academy of Ophthalmology 273

5 Yoshizawa et al Asia-Pacific Journal of Ophthalmology & Volume 1, Number 5, September/October 2012 FIGURE 4. Severe vascular changes in a young patient of CRVO with deteriorating inflammatory conditions. Fundus (A, B) and FA (C, D) findings of CRVO during the preaggravation (A) and postaggravation (BYD) phases in a 16-year-old male adolescent (patient 1). Peripheral retinal vascular sheathing (arrows in B) and extensive vascular leakage with wall staining (arrows in C, D) and nonperfusion areas (C) in the postaggravation status. decreased suddenly to 0.01 at the 4-month follow-up when the dose of PSL was decreased to 15 mg/d. Superficial retinal hemorrhages appeared with marked macular edema and SRD at the posterior pole (Fig. 4B). Retinal veins around the midperiphery showed white sheathing with yellow exudates [Fig. 4B (arrows)]. Late-phase FA revealed nonperfused retinal capillaries extending peripherally from the temporal vascular arcades (Figs. 4C). Notably, retinal vessel wall staining and leakage from the optic disc and retinal vessels were severely increased [Figs. 4C, D (arrows)]. The patient was treated with intravenous FIGURE 5. Effects of systemic corticosteroid treatment on VA and CRT in inflammatory CRVO. Graphs showing changes in the logmar VA (A) and CRT (B). Systemic corticosteroid therapy significantly improved logmar VA (A) and CRT (B) in cases with inflammatory CRVO. *P G * 2012 Asia Pacific Academy of Ophthalmology

6 Asia-Pacific Journal of Ophthalmology & Volume 1, Number 5, September/October 2012 CRVO With Inflammatory Etiology administration of methylprednisolone at 1000 mg/d for 3 days and subsequently with oral PSL with an initial dose of 30 mg/d, which was gradually tapered over 12 months. Retinal hemorrhages and macular edema dramatically reduced. Although laser photocoagulation was applied for capillary nonperfusion, vitreous hemorrhage occurred 8 months after completion of corticosteroid therapy, and thus he underwent pars plana vitrectomy. The concentration of vascular endothelial growth factor in the vitreous fluid markedly elevated to pg/ml. At the final visit, his VA improved to 0.1, and retinal hemorrhages and macular edema completely resolved. DISCUSSION This study revealed clinical features of CRVO with inflammatory etiology represented by anterior vitreous cells and concurrent severe peripheral retinal vascular changes characteristic of occlusive retinal vasculitis. The features were as follows: (1) frequency of approximately 10% in all CRVO cases, (2) distribution across broad age range, (3) male predilection, (4) unknown causative etiology, and (5) good response to systemic corticosteroid therapy. The patients in the present study had severe retinal vascular changes with occluded retinal capillaries in the peripheral region, suggesting the development of occlusive retinal vasculitis exhibiting ischemic CRVO. This peripheral finding together with anterior vitreous cells is not generally observed in typical CRVO associated with arteriosclerotic changes. As concerns the pathogenesis of this disorder, rapid response to systemic corticosteroid therapy together with inflammatory changes suggests an autoimmune process. In a histopathologic study of a CRVO case with marked peripheral retinal leakage, regarded to be equivalent to our present cases, the central retinal vein was obliterated by severe lymphocytic inflammatory infiltration. 14 The pathology of our cases is thought to involve similar inflammatory changes in central retinal vein in addition to peripheral retinal vasculitis. Accordingly, in the present cases, inflammation is likely to extend not only to the central retinal vein, but also to the peripheral retinal vessels causing severe leakage and/or occlusion. Further detailed histopathologic studies are needed to clarify the etiology of this clinical entity. Treatment modalities for ischemic CRVO associated with arteriosclerotic changes have yet to be established. Hayreh 15 described that systemic corticosteroid therapy for ischemic CRVO was used to control macular edema but not venous occlusion itself. Reasonably, retinal hemorrhages in typical ischemic CRVO are not likely to be reduced by systemic corticosteroid therapy that exerts little or no effect on an occluded central retinal vein. In contrast, in the present 6 eyes with inflammatory CRVO diagnosed as ischemic type, high-dose corticosteroids therapy was successful in terms of absorption of retinal hemorrhages in response to the treatment. Moreover, in patient 5, dilated and stagnant retinal capillaries at the posterior pole rapidly normalized after initiation of pulse therapy, suggesting the prompt reperfusion of the occluded central retinal vein. Although IVB and/ or STTA reduced macular edema only transiently by inhibiting vascular hyperpermeability, sustained administration of corticosteroid during several months contributed to the resolution of macular edema as seen in the present cases. Accordingly, these findings suggest that high-dose corticosteroid therapy leads not only to reduction of vascular leakage but also to reperfusion of occluded central retinal vein due to inflammation. In several previous case reports on CRVO with severe peripheral retinal vasculitis resembling our present cases, visual prognosis was extremely poor (no light perception or hand motion) following low-dose oral corticosteroid therapy. 16 In a case with pulse therapy, however, VA finally improved from hand motion to For this subtype of ischemic CRVO with inflammatory conditions, sufficient doses of systemic corticosteroids such as pulse therapy should be recommended. We cannot exclude the possibility of intravitreal triamcinolone acetonide injection as another treatment option to control intraocular inflammation in this subtype of CRVO, although we anticipate that repeated injections together with subsequent ocular complications could be inevitable in this relatively long-term disorder. We performed high-dose systemic corticosteroid therapy in the present cases with intraocular inflammation as well as ordinarily done in severe to moderate cases of uveitis with unknown etiology. The majority of cases (approximately 90%) in their natural course failed to develop the inflammatory findings (Table 1), which indeed needed to be controlled with high-dose systemic corticosteroid therapy. It is reasonable, therefore, to think that common cases with arteriosclerosis-related vaso-occlusive lesions are unlikely to harbor and exhibit such a severe inflammatory property. Differential diagnoses for this clinical entity of inflammatory CRVO are considered to include CRVO in young adults or papillophlebitis. However, these eyes generally exhibit nonischemic CRVO with a self-limiting course and good visual prognosis. The present cases of inflammatory CRVO should be distinguished from CRVO in young adults or papillophlebitis because our patients are distributed across broad age range including the elderly and because they exhibit ischemic CRVO with much poorer visual prognosis. The significance of this clinical entity consists in the possibility of improving visual outcomes by selecting high-dose systemic corticosteroid including pulse therapy despite the old-age onset, which is not usually applied to typical ischemic CRVO associated with arteriosclerosis. Because the pathogenesis involves occlusive retinal vasculitis extending from the central retinal vein to the peripheral region, this subtype of atypical CRVO may therefore be called occlusive papilloretinal vasculitis or inflammatory ischemic CRVO. In conclusion, clinical features in the present cases are characterized by distribution of the disease over broad age range and by favorable responsiveness to high-dose systemic corticosteroid therapy. The frequency of this clinical entity (approximately 10%) is definitely not considered as rare. In clinical practice, patients presenting with CRVO, even if they are middleto old-aged men, should receive thorough examinations as to inflammatory changes including anterior vitreous cells and peripheral retinal changes based on FA. Future studies are needed to accumulate and analyze similar cases. REFERENCES 1. Hansen LL. Retinal vascular disease. In: Joussen AM, Gardner TW, Kirchhof B, et al, eds. Central Retinal Vein Occlusion. New York: Springer; 2007:443Y Elman MJ, Bhatt AK, Quinlan PM, et al. The risk for systemic vascular diseases and mortality in patients with central retinal vein occlusion. Ophthalmology. 1990;97:1543Y Fong AC, Schatz H. 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