Acute inflammation and loss of retinal architecture and function during experimental Bacillus endophthalmitis

Rapid vision loss and explosive inflammation are devastating consequences of Bacillus endophthalmitis that have not been well defined. We therefore analyzed the evolution of intraocular inflammation and loss of retinal architecture and function during experimental Bacillus endophthalmitis. Mice were intravitreally injected with 100 CFU of B. cereus, and eyes were analyzed for bacterial growth, retinal function, architectural changes and retinal cellular stress, inflammatory cytokines, and infiltrating cells. Retinal electrophysiologic and structural changes began as early as 4 to 6 hr postinfection. Significant declines in retinal function paralleled the loss of retinal architecture. Glial fibrillary acidic protein (GFAP) was detected in retina, indicating potential stress. Polymorphonuclear leukocyte (PMN) infiltration into the vitreous began as early as 4 hr postinfection, coinciding with a significant increase in TNF-alpha in the eye. These results indicated that acute inflammation and detrimental architectural and electrophysiologic changes in the retina began earlier than once thought, suggesting that therapeutic intervention should be given at the earliest possible time to avoid vision loss during Bacillus endophthalmitis.     

In vitro Differentiation of Adult Adipose Mesenchymal Stem Cells into Retinal Progenitor Cells

Introduction: It has been previously shown that adult mesenchymal stem cells (MSCs) differentiate into neural progenitor cells (NPCs) and that the differentiation process was completed in 24-48 h. In this previous study, MSCs from a bone marrow or fat source were co-incubated with homologous autoaggressive cells (ECs) against nerve tissue, and these NPCs were successfully used in human regenerative therapeutic approaches. The present study was conducted to investigate whether a similar differentiation method could be used to obtain autologous retinal progenitor cells (RPCs). Methods: Human Th1 cells against retinal tissue were obtained by challenging human blood mononuclear cells with an eye lysate of bovine origin; negative selection was performed using a specific immunomagnetic bead cocktail. Fat MSCs were obtained from a human donor through mechanical and enzymatic dissociation of a surgical sample. The ECs and MSCs were co-cultured in a serum-free medium without the addition of cytokines for 0, 24, 48 and 72 h. The plastic adherent cells were morphologically examined using inverted-phase microscopy and characterized by immunofluorescent staining using antibodies against Pax 6, TUBB3, GFAP, Bestrophin 2, RPE 65, OPN1 SW, and rhodopsin antigens. Results: The early signs of MSC differentiation into RPCs were observed at 24 h of co-culture, and the early differentiated retinal linage cells appeared at 72 h (neurons, rods, Müller cells, retinal ganglion cells and retinal pigmented epithelial cells). These changes increased during further culture. Conclusion: The results reported here support the development of a method to obtain a large number of autologous adult RPCs, which could be used to treat different retinopathies.     

Subretinal transplantation of bone marrow mesenchymal stem cells delays retinal degeneration in the RCS rat model of retinal degeneration

Because there is no effective treatment for this retinal degeneration, potential application of cell-based therapy has attracted considerable attention. Several investigations support that bone marrow mesenchymal stem cells (MSCs) can be used for a broad spectrum of indications. Bone marrow MSCs exert their therapeutic effect in part by secreting trophic factors to promote cell survival. The current study investigates whether bone marrow MSCs secrete factor(s) to promote photoreceptor cell survival and whether subretinal transplantation of bone marrow MSCs promotes photoreceptor survival in a retinal degeneration model using Royal College of Surgeons (RCS) rats. In vitro, using mouse retinal cell culture, it was demonstrated that the conditioned medium of the MSCs delays photoreceptor cell apoptosis, suggesting that the secreted factor(s) from the MSCs promote photoreceptor cell survival. In vivo, the MSCs were injected into the subretinal space of the RCS rats and histological analysis, real-time RT-PCR and electrophysiological analysis demonstrated that the subretinal transplantation of MSCs delays retinal degeneration and preserves retinal function in the RCS rats. These results suggest that MSC is a useful cell source for cell-replacement therapy for some forms of retinal degeneration.     

Neuroprotective effects of angiotensin II type 1 receptor (AT1R) blocker, telmisartan, via modulating AT1R and AT2R signaling in retinal inflammation

PURPOSE: To investigate the retinal neural damage that occurs during inflammation and the therapeutic effects of the angiotensin II type 1 receptor (AT1R) blocker, telmisartan, using a model of endotoxin-induced uveitis (EIU). METHODS: The localization of AT1R and AT2R was shown by immunohistochemistry. EIU was induced by intraperitoneal injection of lipopolysaccharide (LPS). Animals were treated with telmisartan for 2 days and were evaluated 24 hours later. Expression levels of angiotensin II, STAT3 activation induced by inflammatory cytokines, and retinal proteins essential for neural activities (e.g., synaptophysin, rhodopsin) were analyzed by immunoblot. An AT2R antagonist was administered to evaluate the contribution of AT2R signaling in this therapy. Dark-adapted full-field electroretinography (ERG) was also performed. RESULTS: AT1R and AT2R were expressed in presynaptic terminals in most of the retinal neurons. AT1R was also expressed in Müller glial cells. During inflammation, angiotensin II expression was elevated, STAT3 was activated, and synaptophysin and rhodopsin expression were reduced. The expression of glial fibrillary acidic protein (GFAP), downstream of STAT3 activation, was induced in Müller glial cells. However, treatment with telmisartan successfully avoided all these changes. An AT2R antagonist lowered synaptophysin expression despite the treatment. STAT3 activity was negatively correlated with rhodopsin expression. Furthermore, ERG responses, which were mostly prevented by telmisartan, were disturbed during inflammation. CONCLUSIONS: Retinal protein expression and visual function are both disturbed by inflammation. Treatment with the AT1R blocker telmisartan efficiently prevented these signs of retinal neural damage through the reduction of local angiotensin II expression, the blockade of AT1R, and the relative upregulation of AT2R function.     

Effect of Sonic hedgehog gene-modified bone marrow mesenchymal stem cells on graft-induced retinal gliosis and retinal ganglion cells survival in diabetic mice

AIM: To investigate the effects of Sonic hedgehog (Shh) gene-modified bone marrow mesenchymal stem cells (MSCs) on graft-induced retinal gliosis and retinal ganglion cells (RGCs) survival in diabetic mice. METHODS: Bone marrow-derived MSCs were genetically modified with the Shh gene to generate a stably transfected cell line of Shh-modified MSCs (MSC-Shh). Intravitreal injections of MSC-Shh and green fluorescent protein-modified MSCs (MSC-Gfp; control) were administered in diabetic mice. After 4wk, the effects of MSC-Shh on retinal gliosis were evaluated using fundus photography, and markers of gliosis were examined by immunofluorescence and Western blotting. The neurotrophic factors expression and RGCs survival in the host retina were evaluated using Western blotting and immunofluorescence. The mechanisms underlying the effects of MSC-Shh was investigated. RESULTS: A significant reduction of proliferative vitreoretinopathy (PVR) was observed after intravitreal injection of MSC-Shh compared to MSC-Gfp. Significant downregulation of glial fibrillary acidic protein (GFAP) was demonstrated in the host retina after MSC-Shh administration compared to MSC-Gfp. The extracellular signal-regulated kinase 1/2 (ERK1/2), protein kinase B (AKT) and phosphatidylin-ositol-3-kinase (PI3K) pathways were significantly downregulated after MSC-Shh administration compared to MSC-Gfp. Brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) levels were significantly increased in the host retina, and RGCs loss was significantly prevented after MSC-Shh administration. CONCLUSION: MSC-Shh administration reduces graft-induced reactive gliosis following intravitreal injection in diabetic mice. The ERK1/2, AKT and PI3K pathways are involved in this process. MSC-Shh also increases the levels of neurotrophic factors in the host retina and promoted RGCs survival in diabetic mice.     

Mesenchymal stem cells and potential applications in treating ocular disease

Mesenchymal stem cells (MSCs) are remarkable in stem cell biology. Not only do they have significant tissue regeneration potential, but more recently their paracrine effects (either innate or through genetic augmentation) have become increasingly recognized as useful therapeutic approaches. In particular, clinical roles for MSC therapy in neuroprotection and immune suppression are likely to emerge. These therapeutic effects will be particularly advantageous in work on neurological tissues, because MSC-based molecular therapy could overcome some of the difficulties of long-term drug delivery to tissues, such as the eye, which are relatively inaccessible to systemic delivery (for example due to the blood retina barrier). MSC therapy is, therefore, poised for significant impact in ocular molecular therapeutics, particularly for chronic diseases, such as retinal degeneration, glaucoma, and uveitis. Other molecular and tissue regeneration effects of MSCs are also likely to have impact in the management of ocular surface disease and oculoplastics.     

玻璃体腔注射bevacizumab的并发症

玻璃体腔注射bevacizumab治疗多种新生血管性眼病的短期疗效较好,但随着对其研究的不断深入,由玻璃体腔注射的操作过程以及bevacizumab毒性作用等原因引起的一些眼部及全身并发症已逐渐成为临床中不可忽视的问题。就玻璃体腔注射bevacizumab临床应用中出现的并发症,如眼内炎、非感染性眼内炎症反应、一过性眼压升高、结膜下出血、球结膜水肿、视网膜色素上皮（RPE）撕裂、视网膜色素上皮脱离（RPED）、血栓性疾病及子宫不规则出血等进行综述。     

Mesenchymal stromal cells for the treatment of ocular autoimmune diseases

Mesenchymal stromal cells, commonly referred to as MSCs, have emerged as a promising cell-based therapy for a range of autoimmune diseases thanks to several therapeutic advantages. Key among these are: 1) the ability to modulate innate and adaptive immune responses and to promote tissue regeneration, 2) the ease of their isolation from readily accessible tissues and expansion at scale in culture, 3) their low immunogenicity enabling use as an allogeneic “off-the-shelf” product, and 4) MSC therapy's safety and feasibility in humans, as demonstrated in more than one thousand clinical trials. Evidence from preclinical studies and early clinical trials indicate the therapeutic potential of MSCs and their derivatives for efficacy in ocular autoimmune diseases such as autoimmune uveoretinitis and Sjögren's syndrome-related dry eye disease. In this review, we provide an overview of the current understanding of the therapeutic mechanisms of MSCs, and summarize the results from preclinical and clinical studies that have used MSCs or their derivatives for the treatment of ocular autoimmune diseases. We also discuss the challenges to the successful clinical application of MSC therapy, and suggest strategies for overcoming them.     

Changes of the Retina and Intrinsic Survival Signals in a Rat Model of Glaucoma following Brinzolamide and Travoprost Treatments

Purpose: The purpose of this study is to examine the changes of the retina and the intrinsic survival signals of the retina by brinzolamide (Azopt?) and travoprost (Travatan?) in a rat model of chronic ocular hypertension. Methods: Chronic ocular hypertension was induced by cauterization of three episcleral veins. Terminal deoxynucleotidyl transferase-mediated dUTP-nick end-labeling (TUNEL) staining was performed and the expression of glial fibrillary acidic protein (GFAP) was examined to evaluate changes of retinal ganglion cell (RGC) apoptosis and glial cell activation. Western blot analyses of the bcl-2 family and extracellular signal-regulated kinases (ERK) were done to identify changes of the intrinsic survival signaling pathway in the retina. Results: GFAP expression and TUNEL staining revealed significant decreases in RGC apoptosis and glial cell activation after brinzolamide and travoprost administration; bcl-2 and bcl-xL expression were significantly increased after intraocular pressure elevation and it was further increased with brinzolamide and travoprost treatment. This enhancement of survival signaling may have contributed to the decrease in RGC apoptosis. However, the role of ERK signaling was not significant. Conclusions: Decrease in retinal damage and increased intrinsic survival signals suggests the neuroprotective potential of brinzolamide and travoprost in an animal model of chronic ocular hypertension, but further studies are required.     

复明片对视网膜脱离复位术后视神经功能恢复的疗效

目的：评价中药复明片对视网膜脱离复位术后患者视神经功能恢复的疗效。 方法：采用分组对照研究的方法,将我院2010-01/2013-01收治的视网膜脱离复位术患者60例,根据治疗方法随机分为复明片治疗组（观察组）30例和甲钴胺注射液治疗组（对照组）30例。随访6wk,记录并对比分析两组患者视力、眼压、眼底情况以及视网膜神经纤维层厚度（ RNFLT）。 结果：观察组视力、眼底有效率分别为90%,97%,对照组分别为77%,80%,两组比较差异有显著统计学意义（ P〈0.01）。两组患者在治疗后暗适应和明适应ERG a、b波振幅及治疗前后暗适应和明适应a、b波振幅的差值有显著性意义（P〈0.05）,而眼压无明显统计学差异（P〉0.05）。 结论：复明片能促进视网膜复位术后视网膜下液体的吸收,促进视神经恢复,改善视功能。     

银杏叶提取物联合灯盏细辛对视网膜神经节细胞的保护作用

目的:探讨银杏叶提取物联合灯盏细辛对兔慢性高眼压模型视网膜神经节细胞的保护作用。方法:采用α-糜蛋白酶(0.2mL)(2667.2μkat)注入家兔眼后房,造成实验性慢性高眼压。将造模成功的32只家兔随机分为4组,每组8只,分别给予以下治疗:银杏叶提取物150mg/kg(银杏叶组);灯盏细辛150mg/kg(灯盏细辛组);银杏叶提取物联合灯盏细辛皆灌胃,1次/d银杏叶提取加灯盏细辛(联合用药组);不做任何治疗(模型对照组)。4wk后各组分别进行视网膜神经节细胞凋亡检测正常视神经节细胞计数和光镜观察视网膜各层病理改变。结果:每组均可观察到阳性细胞,正常神经节细胞计数最多为联合用药组(889.00±40/mm2)、最少为模型对照组(581±24/mm2),P<0.01,光镜下模型对照组视网膜各层结构最紊乱,联合用药组视网膜各层组织最完整。结论:银杏叶提取物联合灯盏细辛能阻止高眼压导致视网膜神经节细胞发生凋亡。     

胶质纤维酸性蛋白在青光眼大鼠视网膜神经胶质细胞中的表达

目的:探讨胶质纤维酸性蛋白(GFAP)在青光眼大鼠视网膜Müler细胞上的诱导表达情况及可能的意义。方法:采用烧灼涡静脉的方法制作大鼠青光眼模型,分别于术后2h;1,3d;1,2,3wk取材,制作视网膜矢状位冰冻切片和视网膜铺片,进行GS/GFAP免疫荧光双标。提取视网膜总蛋白行GFAP免疫印迹半定量分析。结果:视网膜矢状位切片可见,正常大鼠视网膜中,GFAP阳性染色只出现在神经节细胞层的星形胶质细胞上,而Müller细胞不表达GFAP。制作青光眼模型术后2h,Müller细胞上出现GFAP阳性染色,术后1,3d,GFAP的表达显著增加,到术后1wk,GFAP在Müller细胞上的表达量达到高峰,一直持续到术后3wk,免疫印迹半定量分析与以上结果吻合。术后1wk视网膜铺片中清晰可见Müller细胞足板出现GFAP的诱导表达。结论:高眼压时GFAP在Müller细胞上的诱导表达尤其在足板处的强烈表达是Müller细胞对眼压升高产生的一种反应,GFAP可能是一种潜在的有用的生物标记物。     

Trends in using mesenchymal stromal/stem cells (MSCs) in treating corneal diseases

Since their inception in the 1960s–70s, mesenchymal stem/stromal cells (MSCs) have gained interest because of their differentiation potential, anti-inflammatory effects, and immune-modulating properties. Both cell-based and cell-free MSC treatments show healing capacity in injured tissues. Cell-based treatment comprises MSCs and all secreted products, whereas cell-free treatments include only the secreted products. MSCs are therapeutically administered to many damaged organs owing to their efficacy. Specifically, the eye is a unique organ system to study the effects of MSCs, as treatment is easily applied and measured owing to its external location. The eye holds an immune-privileged status, wherein inflammation and immune responses are innately down-regulated. As excessive inflammation in the cornea often leads to fibrosis and irreversible corneal hazing, many studies have investigated the anti-inflammatory and immune-modulating capacities of MSCs. Decades of research suggest that MSCs modulate the immune response by secreting cytokines, growth factors, and extracellular matrix proteins that inhibit the infiltration of inflammatory cells following injury and promote a healing phenotype via M2 macrophage polarization. MSCs have also shown trans-differentiation potential into cornea-specific cell types during the wound healing process, such as corneal epithelial, stromal, or endothelial cells. This review discusses recent investigations of MSC treatment in the cornea, focusing on therapeutic efficacy, mechanisms, and future directions.     

Tuberculin skin testing in uveitis patients and treatment of presumed intraocular tuberculosis in Japan

PURPOSE: To evaluate the results of tuberculin skin testing in Japanese patients with intraocular inflammation and to assess the outcome of treatment for presumed intraocular tuberculosis in selected patients. DESIGN: Prospective, noncomparative, interventional case series. PARTICIPANTS: One hundred twenty-six patients, newly referred to the Ocular Inflammation Service at the Kyorin Eye Center from April 1998 to August 2000, underwent systemic evaluation for the diagnosis and/or treatment of uveitis. METHODS: Tuberculin skin testing with purified protein derivative was performed as part of the systemic evaluation. The diagnosis of presumed intraocular tuberculosis was made when findings were consistent with possible intraocular tuberculosis, the tuberculin skin test was positive (induration more than 10 mm), and no other cause of uveitis was suggested by symptoms, signs, or ancillary testing. Using these criteria, 10 patients were given a diagnosis of presumed intraocular tuberculosis and treated with antituberculosis therapy consisting of isoniazid, with or without rifampicin. Some of these patients also received a tapered course of oral corticosteroids after the initiation of antituberculosis treatment. None of the patients had any signs or symptoms of acquired immunodeficiency syndrome. MAIN OUTCOME MEASURES: Visual acuity and ophthalmologic examination to assess degree of intraocular inflammation. RESULTS: Twenty-six of the 126 patients (20.6%) had a positive tuberculin skin test result. Ten of these 26 patients (38.5%) were treated for a diagnosis of presumed intraocular tuberculosis. Nine patients had no evidence of pulmonary tuberculosis, and one patient had presumed tuberculous hilar lymphadenitis. The predominant clinical finding was choroidal or optic disc nodule in three patients, retinal vasculitis in three patients, and choroiditis in four patients. Nine patients exhibited decreased intraocular inflammation with treatment. CONCLUSIONS: Roughly one fifth of the uveitis patients who underwent systemic evaluation had a positive tuberculin skin test result, and 9 of 10 selected skin test-positive patients with clinical findings consistent with intraocular tuberculosis had a favorable response to antituberculosis therapy. These results suggest that intraocular tuberculosis continues to be a major diagnostic consideration for uveitis patients in Japan.     

A review of evidence guiding the use of corticosteroids in the treatment of intraocular inflammation

PURPOSE: To review the published laboratory and clinical studies pertaining to the efficacy of corticosteroids in the treatment of intraocular inflammation. METHODS: A Pubmed computer search was conducted of all publications focusing on the efficacy of corticosteroids in treating ocular inflammation, with an additional search of pertinent citations culled from these articles. RESULTS: Experimental evidence has established the efficacy of corticosteroid eyedrops in treating intraocular inflammation. The effectiveness of periocular corticosteroid injections as well as of systemic corticosteroids is supported by extensive clinical experience, although placebo-controlled trials are lacking. Few studies have documented differences in efficacy between the common corticosteroid agents or between the different routes of administration. Subconjunctival injection appears to achieve higher intraocular corticosteroid levels than do other routes of periocular injection or systemic therapy. Clinical experience with intravitreous corticosteroid injection is insufficient to firmly attest to its efficacy or safety. CONCLUSION: The efficacy of corticosteroids in treating intraocular inflammation is based on limited experimental evidence and considerable clinical experience.     

MSC移植对缺血再灌注损伤视网膜神经节细胞Bcl-2/Bax表达的影响

目的研究骨髓间充质干细胞(mesenchymal stem cells,MSC)移植对视网膜缺血再灌注损伤(retinal ischemia-reperfusion injury,RIRI)视网膜神经节细胞Bcl-2/Bax表达的影响,为MSC移植治疗RIRI提供实验依据。方法 44只SD大鼠分为正常组(4只)、模型组(20只)、MSC移植组(20只)。前房加压法建立大鼠RIRI模型。体外培养大鼠MSC,MSC移植组于再灌注后予以玻璃体腔注射MSC。免疫组织化学法检测各组大鼠视网膜缺血再灌注2h、6h、12h、24h、48h后Bcl-2/Bax表达情况。结果正常组视网膜神经节细胞未见Bcl-2、Bax表达。再灌注后2h、6h、12h、24h、48h,模型组Bcl-2表达分别为0.280±0.008、0.323±0.010、0.474±0.020、0.451±0.011、0.407±0.011,MSC移植组Bcl-2表达分别为0.340±0.006、0.401±0.009、0.610±0.006、0.581±0.009、0.490±0.005;模型组Bax表达分别为0.322±0.007、0.457±0.010、0.469±0.022、0.591±0.014、0.529±0.010,MSC移植组分别为0.252±0.008、0.366±0.011、0.389±0.009、0.433±0.013、0.391±0.004。MSC移植组与模型组比较Bcl-2表达均明显增强(均为P<0.01),Bax表达均明显减弱(均为P<0.01)。结论 RIRI大鼠行MSC移植术,可使神经节细胞Bcl-2表达增强,Bax表达减弱,Bcl-2/Bax比值升高,减少神经节细胞凋亡。MSC移植对RIRI神经节细胞有明显的保护作用。     

Failure of intravitreal dexamethasone to diminish inflammation or retinal toxicity in an experimental model of Bacillus cereus endophthalmitis

PURPOSE: To determine whether the usual clinical dose of intravitreal dexamethasone can attenuate intraocular inflammation and retinal necrosis in a rabbit model of fulminant Bacillus cereus endophthalmitis induced by crude exotoxins. METHODS: Thirty-six eyes from pigmented mongrel rabbits received intravitreal injections of varying concentrations of crude B. cereus exotoxins with or without concomitant injections of 400 microg of dexamethasone sodium phosphate (0.1% solution). After ophthalmoscopic examination at 4 or 18 hr postinjection, the animals were killed and histopathologic findings graded. RESULTS: Intraocular inflammation and retinal necrosis scores in eyes receiving both exotoxins and dexamethasone did not differ significantly from eyes receiving exotoxins alone for any exotoxin dose at 4 or 18 hr. The severity of retinal necrosis increased with toxin dose and was nearly maximal after 4 hr. Intraocular inflammation also generally increased with dose, but continued to increase until 18 hr. CONCLUSIONS: Standard clinical doses of intravitreal dexamethasone do not appear to attenuate the intraocular inflammatory or tissue response to secreted B. cereus exotoxins. Other treatment modalities including vitrectomy, to decrease exotoxin load, and exotoxin inhibitors may be necessary for the effective treatment of B. cereus endophthalmitis.     

地塞米松缓释微粒在增生性玻璃体视网膜病变的应用

目的：观察含地塞米松（DEX）的缓释微粒治疗增生性玻璃体视网膜病变（PVR）的临床疗效。方法：9例（9只眼）视网膜脱离伴PVR患者进行常规玻璃体视网膜手术，并在玻璃体腔内植入1粒DEX微粒（含地塞米松1mg），观察术后反应及视力、PVR发展、DEX的位置及形状变化等。结果：术后炎症反应轻，7只眼视网膜复位，3只眼后极部视网膜前有增生；2只眼视网膜局限性脱离，最终3只眼玻璃腔内硅油填充。随访视力有8只眼较术前提高（P=0.015）。DEX未见对视网膜有不良影响，仅在随着处有少量色素吸附，4-6月后吸收。结论：DEX抑制PVR术后炎症反应及较远期作用是安全、有效的；对手术未完全清除的视网膜前增生有一定的抑制作用。     

Overview and Diagnosis of Acute Retinal Necrosis Syndrome

Acute retinal necrosis (ARN) syndrome, also known as Kirisawa's uveitis, is one of the most serious ocular diseases, and is characterized by a combination of peripheral, confluent, necrotizing retinitis, retinal arteritis, and intraocular inflammation. ARN syndrome is caused by the herpesvirus family, including herpes simplex virus (HSV) and varicella-zoster virus (VZV). The diagnosis of ARN syndrome is fundamentally based on clinical appearance and the demonstration of viral infection. Recently, polymerase chain reaction techniques permit detection of very small amounts of viral DNA in intraocular specimens. This knowledge can help in both the diagnosis and design of therapeutic strategy for ARN syndrome. Here we review the clinical presentation and the current advances in the diagnosis of ARN syndrome.     

Overview and diagnosis of acute retinal necrosis syndrome

Acute retinal necrosis (ARN) syndrome, also known as Kirisawa's uveitis, is one of the most serious ocular diseases, and is characterized by a combination of peripheral, confluent, necrotizing retinitis, retinal arteritis, and intraocular inflammation. ARN syndrome is caused by the herpesvirus family, including herpes simplex virus (HSV) and varicella-zoster virus (VZV). The diagnosis of ARN syndrome is fundamentally based on clinical appearance and the demonstration of viral infection. Recently, polymerase chain reaction techniques permit detection of very small amounts of viral DNA in intraocular specimens. This knowledge can help in both the diagnosis and design of therapeutic strategy for ARN syndrome. Here we review the clinical presentation and the current advances in the diagnosis of ARN syndrome.