Outcomes of standalone ab interno trabeculotomy in the treatment of open-angle glaucoma in eyes with high myopia.

BACKGROUND: We retrospectively evaluate the long-term efficacy and safety of trabeculotomy glaucoma surgery in treating open-angle glaucoma (OAG) in eyes with high myopia (HM). METHODS: This study included 20 eyes with HM (axial length ≥ 26.5 mm) and OAG; age, preoperative IOP (intraocular pressure), and sex-matched 20 non-HM eyes (axial length < 26.5 mm) served as controls. Each eye underwent standalone ab interno trabeculotomy using a Kahook dual blade. A follow-up examination was performed 36 months after surgery. The main outcome measure was the operative success rate (i.e., a ≥ 20% pre- to post-operative reduction in IOP with or without IOP-lowering medication). Kaplan-Meier analysis was employed as a measure of surgical success. The secondary outcome measures were postoperative IOP, the number of glaucoma medications, and postoperative complications. RESULTS: IOP and the number of glaucoma medications were statistically significantly reduced at all postoperative follow-up examinations. The Kaplan-Meier analysis demonstrated that the probability of postoperative success at 36 months was 45% and 65% for HM and non-HM eyes, respectively. In the HM group, the presence of pathological myopia was statistically significant risk factor for surgical failure. No critical postoperative complications were detected. CONCLUSIONS: In our study, the long-term efficacy of ab interno trabeculotomy in HM eyes with OAG was inferior to that in non-HM eyes with OAG. Our findings suggest that surgical indications for trabeculotomy in HM should be determined based on the presence of pathological myopia.

CORRELATIONS BETWEEN EXPERIMENTAL MYOPIA MODELS AND HUMAN PATHOLOGIC MYOPIA.

PURPOSE: To analyze the hallmark features of pathologic myopia developed in animal models and compare them with those seen in patients. METHODS: A literature review was performed to identify animal models that exhibited key features of pathologic myopia, namely posterior staphyloma, myopic maculopathy, lacquer cracks, and choroidal neovascularization, either spontaneously or induced by monocular deprivation. Using imaging modalities, such as optical coherence tomography, confocal scanning laser ophthalmoscopy, fluorescein angiography, and electron microscopy, these features were compared with those found in myopic maculopathy of patients. RESULTS: Three types of animals were identified. The LRP2 knockout mice exhibited posterior staphylomas and chorioretinal atrophy at 21 and 60 days after birth, respectively. Retinopathy globe enlarged (rge) chicks and normal lid-sutured chicks developed lacquer cracks and chorioretinal atrophy. Lacquer cracks detected in rge chicks subsequently progressed to patchy chorioretinal atrophy, which is also commonly seen in patients with pathologic myopia. CONCLUSION: The LRP2 knockout mice, retinopathy globe enlarged (rge) chicks, and normal lid-sutured chicks exhibit features typical for myopic maculopathy in patients and could serve to further elucidate the pathogenesis of myopic maculopathy.

Role of IL-22- and TNF-α-producing Th22 cells in uveitis patients with Behcet's disease.

Behçet's disease is a systemic inflammatory disorder with recurrent episodes of oral ulceration, skin lesions, genital ulceration, and intraocular inflammation (uveitis). The intraocular inflammation is strictly associated with Th effector cells. IL-22 is a member of the IL-10 cytokine family that is involved in inflammatory processes. Recently, Th22 cells were identified as a Th cell population that produces IL-22 and TNF-α and are distinct from Th1, Th2, and Th17 cells. In this study, we established Th22-type T cell clones from ocular samples taken from Behçet's disease patients with active uveitis. These clones produced large amounts of IL-22 and TNF-α but not the Th1 cytokine IFN-γ and the Th17 cytokine IL-17. CD4(+) T cells from the peripheral blood of Behçet's disease patients differentiated into Th22 cells in the presence of IL-6 and TNF-α in vitro. The polarized Th22 cell lines produced large amounts of IL-22, and the polarized Th1 and Th17 cells also produced IL-22. In the presence of anti-TNF-α- and anti-IL-6-blocking Abs, Behçet's disease Th22-type T cells failed to produce IL-22. In addition, infliximab-pretreated Th22 cells and Th22-type ocular T cells produced less IL-22 and TNF-α. Moreover, IL-22-producing T cells were isolated from mice with experimental autoimmune uveitis, an animal model of Behçet's disease, and the intraocular T cells from uveitis models produced large amounts of IL-22 in the presence of retinal Ags. Our results suggest that inflammatory cytokines IL-22 and TNF-α may play a key role in the ocular immune response in Behçet's disease.

Bilateral hearing impairment as the initial symptom of sympathetic ophthalmia.

IMPORTANCE: Sympathetic ophthalmia (SO), a rare bilateral panuveitis following penetrating ocular trauma or ocular surgery to one eye, shares a strikingly similar ocular pathology to that of Vogt-Koyanagi-Harada disease (VKH). Audiovestibular dysfunction is a major extraocular manifestation of VKH; however, to date, only a few cases of sympathetic ophthalmia associated with hearing loss have been reported from ophthalmologists, but not otolaryngologists. Accordingly, little is known about the audiovestibular findings in patients with SO. We herein present two cases of SO with preceding bilateral hearing loss. OBSERVATIONS: The patient in Case 1, an 80-year-old female, experienced acute bilateral hearing loss. Five days after the onset of hearing loss, she presented with sudden bilateral blurred vision. In Case 2, a 32-year-old female noticed acute bilateral hearing loss and also experienced acute bilateral blurred vision the subsequent day. Patient 1 had a history of a penetrating injury to the right eye 25 days before the onset of hearing loss, while patient 2 had previously undergone right vitreous surgery twice for the treatment of a myopic macular hole and retinal detachment 36 and 43 days prior to the current symptom onset. Both cases were diagnosed as SO based on ocular findings of bilateral panuveitis and the history of ocular insult. Patient 1 carried HLA-DR4, HLA-DR15, HLA-A33, HLA-A24, HLA-B44 and HLA-B52, and patient 2 carried HLA-DR4. Audiograms showed bilateral mild to moderate sensorineural hearing loss in both cases, with normal auditory brainstem responses and deteriorated distortion product otoacoustic emission amplitudes. In addition, the significant recruitment phenomenon observed in case 1 suggested a cochlear origin of the hearing loss. Both patients received corticosteroid therapy, and the cochlear signs and symptoms recovered within one month. CONCLUSIONS AND RELEVANCE: This is the first report to describe the comprehensive audiovestibular findings in patients with SO. In the present study, acute bilateral hearing loss developed a couple of days prior to the onset of bilateral visual loss and auditory examinations suggested a cochlear etiology in both cases.

Blue Wavelength of Scanning Laser Ophthalmoscope Potentially Detects Arteriosclerotic Lesions in Diabetic Retinopathy.

(1) Background: The fundus examination is one of the best and popular methods in the assessment of vascular status in the human body. Direct viewing of retinal vessels by ophthalmoscopy has been utilized in judging hypertensive change or arteriosclerosis. Recently, fundus imaging with the non-mydriatic scanning laser ophthalmoscope (SLO) has been widely used in ophthalmological clinics since it has multimodal functions for optical coherence tomography or angiography with contrast agent dye. The purpose of this study was to examine the utility in detecting arteriosclerosis of retinal vessels in SLO images; (2) Methods: Both color and blue standard field SLO images of eyes with diabetic retinopathy (DR) were examined retrospectively. Retinal arteriosclerosis in color SLO images was graded according to the Scheie classification. Additionally, characteristics of retinal arterioles in blue SLO images were identified and examined for their relevance to arteriosclerosis grades, stages of DR or general complications; (3) Results: Relative to color fundus images, blue SLO images showed distinct hyper-reflective retinal arterioles against a monotone background. Irregularities of retinal arterioles identified in blue SLO images were frequently observed in the eyes of patients with severe arteriosclerosis (Grade 3: 79.0% and Grade 4: 81.8%). Furthermore, the findings on arterioles were more frequently associated with the eyes of DR patients with renal dysfunction (p < 0.05); (4) Conclusions: While color SLO images are equally as useful in assessing retinal arteriosclerosis as photography or ophthalmoscopy, the corresponding blue SLO images show arteriosclerotic lesions with high contrast in a monotone background. Retinal arteriosclerosis in eyes of advanced grades or advanced DR frequently show irregularities of retinal arterioles in the blue images. The findings of low, uneven, or discontinuous attenuation were easier to find in blue than in color SLO images. Consequently, blue SLO images can show pathological micro-sclerosis in retinal arterioles and are potentially one of the safe and practical methods for the vascular assessment of diabetic patients.

Characteristics of physical activity during beginner-level group tennis lessons and the effect daily activity.

Tennis is a popular leisure sport, and studies have indicated that playing tennis regularly provides many health benefits. We aimed to clarify the characteristics of physical activity during beginner-level group tennis lessons and daily physical activity of the participants. Physical activity was measured using an accelerometer sensor device for four weeks, including the 80-min duration tennis lessons held twice a week. Valid data were categorized for tennis and non-tennis days. The mean physical activity intensity during the tennis lesson was 3.37 METs. The mean ratio of short-bout rest periods to the tennis lesson time in 90 and 120 s was 7% and 4%, respectively. The mean physical activity intensity was significantly higher (p < 0.0001) and the duration of vigorous-intensity physical activity (VPA) was increased in 76% of participants on days with tennis lessons compared to without tennis lessons. Beginner-level tennis lesson has characteristics of less short-bout rest physical activity than previously reported competitive tennis match and increased the duration of VPA in daily activity compared to without tennis lessons, suggesting that beginner-level tennis lessons contribute physical activity of health benefits.

Microperimetry in Retinal Diseases.

Retinal microperimetry (MP) is a procedure that assesses the retinal sensitivity while the fundus is directly observed, and an eye tracker system is active to compensate for involuntary eye movements during testing. With this system, the sensitivity of a small locus can be accurately determined, and it has become an established ophthalmic test for retinal specialists. Macular diseases are characterized by chorioretinal changes; therefore, the condition of the retina and choroid requires careful and detailed evaluations to perform effective therapy. Age-related macular degeneration is a representative retinal disease in which the macular function has been evaluated by the visual acuity throughout the course of the disease process. However, the visual acuity represents the physiological function of only the central fovea, and the function of the surrounding macular area has not been sufficiently evaluated throughout the different stages of the macula disease process. The new technique of MP can compensate for such limitations by being able to test the same sites of the macular area repeatedly. This is especially useful in the recent management of age-related macular degeneration or diabetic macular edema during anti-vascular endothelial growth factor treatments because MP can assess the effectiveness of the treatment. MP examinations are also valuable in diagnosing Stargardt disease as they can detect visual impairments before any abnormalities are found in the retinal images. The visual function needs to be carefully assessed along with morphologic observations by optical coherence tomography. In addition, the assessment of retinal sensitivity is useful in the presurgical or postsurgical evaluations.

Retinoic acid from retinal pigment epithelium induces T regulatory cells.

Primary cultured retinal pigment epithelial (RPE) cells can convert T cells into T regulatory cells (Tregs) through inhibitory factor(s) including transforming growth factor ß (TGFß) in vitro. Retinoic acid (RA) enhances induction of CD4(+) Tregs in the presence of TGFß. We investigated whether RA produced by RPE cells can promote generation of Tregs. We found that in vitro, RA-treated T cells expressed high levels of Foxp3 in the presence of recombinant TGFß. In GeneChip analysis, cultured RPE cells constitutively expressed RA-associated molecules such as RA-binding proteins, enzymes, and receptors. RPE from normal mice, but not vitamin A-deficient mice, contained significant levels of TGFß. RPE-induced Tregs from vitamin A-deficient mice failed to suppress activation of target T cells. Only a few Foxp3(+) T cells were found in intraocular cells from vitamin A-deficient experimental autoimmune uveitis (EAU) mice, whereas expression was higher in cells from normal EAU mice. RA receptor antagonist-pretreated or RA-binding protein-siRNA-transfected RPE cells failed to convert CD4(+) T cells into Tregs. Our data support the hypothesis that RPE cells produce RA, thereby enabling bystander T cells to be converted into Tregs through TGFß promotion, which can then participate in the establishment of immune tolerance in the eye.

Progress of Imaging in Diabetic Retinopathy-From the Past to the Present.

Advancement of imaging technology in retinal diseases provides us more precise understanding and new insights into the diseases' pathologies. Diabetic retinopathy (DR) is one of the leading causes of sight-threatening retinal diseases worldwide. Colour fundus photography and fluorescein angiography have long been golden standard methods in detecting retinal vascular pathology in this disease. One of the major advancements is macular observation given by optical coherence tomography (OCT). OCT dramatically improves the diagnostic quality in macular edema in DR. The technology of OCT is also applied to angiography (OCT angiograph: OCTA), which enables retinal vascular imaging without venous dye injection. Similar to OCTA, in terms of their low invasiveness, single blue color SLO image could be an alternative method in detecting non-perfused areas. Conventional optical photography has been gradually replaced to scanning laser ophthalmoscopy (SLO), which also make it possible to produce spectacular ultra-widefield (UWF) images. Since retinal vascular changes of DR are found in the whole retina up to periphery, it would be one of the best targets in UWF imaging. Additionally, evolvement of artificial intelligence (AI) has been applied to automated diagnosis of DR, and AI-based DR management is one of the major topics in this field. This review is trying to look back on the progress of imaging of DR comprehensively from the past to the present.

Sympathetic ophthalmia in eye with pathologic myopia.

PURPOSE: To present our findings in a case of SO that developed in an eye with pathologic myopia. OBSERVATIONS: The patient was an 83-year-old woman who was examined one month after an ocular trauma to the right eye. She was found to have signs of uveitis with multiple serous retinal detachments in the non-injured contralateral left eye. In addition, she had hearing loss and mononuclear pleocytosis of the spinal fluids. Swept-source OCT images showed focal and choroidal thickening in areas with abrupt edges that was restricted to the regions with more normal appearing choroid. Bruch's membrane was damaged at the edge of the focal choroidal thickening. The ocular and systemic findings were rapidly resolved after systemic corticosteroid therapy. CONCLUSIONS AND IMPORTANCE: The pathobiological and clinical course of SO is nearly identical to Vogt-Koyanagi Harada disease (VKH) although its pathogenesis of autoimmunity had not been definitively established. In eyes with pathologic myopia, the choroid is extremely thin and sometimes completely absent. The findings in this rare case indicate that in eyes with thin choroid, the OCT findings typical of SO might be different from those seen in non-highly myopic eyes. Thus, the pre-status of the choroid may affect the choroidal thickening in pathological conditions. This case gives us a valuable insight in understanding the pathology of SO and characteristic of pathologic myopia.

Acquisition of T regulatory function in cathepsin L-inhibited T cells by eye-derived CTLA-2alpha during inflammatory conditions.

Pigment epithelium isolated from the eye possesses immunosuppressive properties such as regulatory T (Treg) cell induction; e.g., cultured retinal pigment epithelium (RPE) converts CD4(+) T cells into Treg cells in vitro. RPE constitutively expresses a novel immunosuppressive factor, CTLA-2alpha, which is a cathepsin L (CathL) inhibitor, and this molecule acts via RPE to induce Treg cells. To clarify CTLA-2alpha's role in the T cell response to RPE in ocular inflammation, we used the experimental autoimmune uveitis (EAU) animal model to examine this new immunosuppressive property of RPE. In EAU models, TGF-beta, but not IFN-gamma inflammatory cytokines, promotes the up-regulation of the expression of CTLA-2alpha in RPE. Similarly, CTLA-2alpha via RPE was able to promote TGF-beta production by the CD4(+) T cells. The RPE-exposed T cells (RPE-induced Treg cells) greatly produced TGF-beta and suppressed bystander effector T cells. There was less expression of CathL by the RPE-exposed T cells, and CathL-inhibited T cells were able to acquire the Treg phenotype. Moreover, CathL-deficient mice spontaneously produced Treg cells, with the increase in T cells potentially providing protection against ocular inflammation. More importantly, CD4(+) T cells from EAU in CathL knockout mice or rCTLA-2alpha from EAU animals were found to contain a high population of forkhead box p3(+) T cells. In both EAU models, there was significant suppression of the ocular inflammation. These results indicate that RPE secretes CTLA-2alpha, thereby enabling the bystander T cells to be converted into Treg cells via TGF-beta promotion.

Blue Widefield Images of Scanning Laser Ophthalmoscope Can Detect Retinal Ischemic Areas in Eyes With Diabetic Retinopathy.

PURPOSE: To determine whether the hyporeflective areas in the blue images obtained by widefield scanning laser ophthalmoscopy (SLO) correspond to the non-perfused areas (NPAs) in the fluorescein angiograms (FA) in eyes with diabetic retinopathy (DR). DESIGN: Retrospective observational case series. METHODS: Ninety patients with diabetes mellitus (DM) were studied. All had undergone multicolor widefield SLO imaging. The NPAs in the FA images and hyporeflective areas in the blue widefield SLO images were examined. The morphology of the retina was determined by optical coherence tomography. RESULTS: Hyporeflective areas in the blue SLO images were found with a rate of 76.6% in eyes with proliferative DR eyes. In a comparison of the hyporeflective areas of the blue SLO images to the non-perfused areas in the FA images, the appearance and the correspondence in the locations of these two types of images were found, and the rate was highly concordant with a Cohen's kappa value of 0.675. CONCLUSIONS: The high concordance between the hyporeflective areas in the widefield blue SLO and the NPAs in the FA indicates that widefield blue SLO can be used to identify ischemic retinal areas in eyes with DR without the intravenous injection of any dye.

Human retinal pigment epithelium-induced CD4+CD25+ regulatory T cells suppress activation of intraocular effector T cells.

Murine retinal pigment epithelial (RPE) cells suppress T-cell activation by releasing soluble inhibitory factors and promote the generation of regulatory T cells in vitro. These T cells exposed to RPE supernatants (RPE-induced Treg cells) can suppress the activation of bystander effector T cells via the production of transforming growth factor-beta (TGFbeta). In the present study, we showed that human RPE-induced Treg cells are also able to acquire regulatory function when human RPE cell lines were pretreated with recombinant TGF beta 2. These RPE-induced Treg cells produced TGF beta 1 and IL-10 but not IFN gamma, and they significantly suppressed the activation of target cell lines and intraocular T-cell clones established from patients with active uveitis. Moreover, CD4(+)CD25(+) RPE-induced Treg cells expressed CTLA-4 and Foxp3 molecules, and the CD25(+) Treg cells profoundly suppressed the T-cell activation. Thus, in vitro manipulated Treg cells acquire functions that participate in the establishment of immune tolerance in the eye.

Retinal pigment epithelium-derived CTLA-2alpha induces TGFbeta-producing T regulatory cells.

T cells that encounter ocular pigment epithelium in vitro are inhibited from undergoing TCR-triggered activation, and instead acquire the capacity to suppress the activation of bystander T cells. Because retinal pigment epithelial (RPE) cells suppress T cell activation by releasing soluble inhibitory factors, we studied whether soluble factors also promote the generation of T regulatory (Treg) cells. We found that RPE converted CD4(+) T cells into Treg cells by producing and secreting CTLA-2alpha, a cathepsin L (CathL) inhibitor. Mouse rCTLA-2alpha converted CD4(+) T cells into Treg cells in vitro, and CTLA-2alpha small interfering RNA-transfected RPE cells failed to induce the Treg generation. RPE CTLA-2alpha induced CD4(+)CD25(+)Foxp3(+) Treg cells that produced TGFbeta in vitro. Moreover, CTLA-2alpha produced by RPE cells inhibited CathL activity in the T cells, and losing CathL activity led to differentiation to Treg cells in some populations of CD4(+) T cells. In addition, T cells in the presence of CathL inhibitor increased the expression of Foxp3. The CTLA-2alpha effect on Treg cell induction occurred through TGFbeta signaling, because CTLA-2alpha promoted activation of TGFbeta in the eye. These results show that immunosuppressive factors derived from RPE cells participate in T cell suppression. The results are compatible with the hypothesis that the eye-derived Treg cells acquire functions that participate in the establishment of immune tolerance in the posterior segment of the eye.

Suboptimal therapy controls clinically apparent disease but not subclinical progression of Vogt-Koyanagi-Harada disease.

PURPOSE: To evaluate clinical and angiographic differences in patients with Vogt-Koyanagi-Harada (VKH) disease during the early 4-month treatment phase with high- or medium-dose systemic corticosteroid therapy. METHODS: VKH patients treated at the Centre for Ophthalmic Specialized Care, Lausanne, Switzerland (n = 4), or the Department of Ophthalmology, Tokyo Medical and Dental University, Tokyo, Japan (n = 5), underwent a pre-treatment indocyanine green angiography (ICGA) and a follow-up ICGA four months after treatment began. Lausanne patients received high-dose, systemic corticosteroid therapy, with or without immunosuppressive therapy. Tokyo patients received medium-dose systemic corticosteroid therapy that included 3 days of intravenous pulse methylprednisolone. ICGA signs including choroidal stromal vessel hyperfluorescence and leakage, hypofluorescent dark dots (HDD), fuzzy vascular pattern of large stromal vessels and disc hyperfluorescence were retrospectively compared. RESULTS: The pre-treatment ICGA demonstrated that each of the nine patients had choroidal inflammatory foci, as indicated by HDD. At 4-month follow-up, clinical and fluorescein findings had improved almost equally in both groups. HDD had resolved in the Lausanne group but persisted in the Tokyo group. Sunset glow fundus occurred in three of the Tokyo patients and none of the Lausanne patients. CONCLUSIONS: Submaximal doses of inflammation suppressive therapy are sufficient to suppress clinically apparent disease but not the underlying lesion process. This explains the propensity for sunset glow fundus in seemingly controlled disease.

A 10-year follow-up of infliximab monotherapy for refractory uveitis in Behçet's syndrome.

Infliximab (IFX) was the first biologic introduced for refractory uveitis treatment in Behçet's syndrome (BS). However, there have been few reports on the safety and efficacy of IFX monotherapy over follow-up periods of more than 10 years. This retrospective study evaluated the 10-year safety and efficacy of IFX monotherapy compared to IFX combination therapies with colchicine or corticosteroid for refractory uveitis in BS patients. Monotherapy was performed in 30 eyes of 16 patients while combination therapies were performed in 20 eyes of 11 patients. Continuation of IFX occurred in 70.3% of enrolled patients for 10 years without any significant difference noted in the retention rate between the monotherapy and combination therapies (p = 0.86). Reduction of ocular inflammatory attacks and improvement of best corrected visual acuity occurred in the monotherapy group after 10 years, which was equivalent to that for the combination therapies. Although adverse events (AEs) or therapy discontinuation occurred during the initial 5 years in both therapies, no AEs were observed for either therapy after 6 years. Our results suggested that IFX monotherapy proved to be effective and not inferior to combination therapies over a 10-year follow-up. Although loss of response and AEs may be noticed during the initial 5-year period, a safe and effective continuation can be expected thereafter.

Human iris pigment epithelium suppresses activation of bystander T cells via TGFbeta-TGFbeta receptor interaction.

Iris pigment epithelial (IPE) cells from the anterior segment in the eye are able to suppress activation of bystander responder T cells in vitro. The cultured IPE cells fully suppress proliferation and cytokine production by responder T cells via direct cell-to-cell contact. We have now investigated whether primary cultured human iris pigment epithelial (h-IPE) cells that were established from fresh iris tissues can also inhibit the activation of T cells in vitro. We found that cultured h-IPE cells significantly inhibited T cell proliferation and the IFN-gamma production by the target T cells from both the allogeneic and autogeneic peripheral blood mononuclear cells (PBMCs). The h-IPE cells also inhibited the activation of CD4(+) T cells from patients with active uveitis. The suppression by h-IPE occurred in a completely contact-dependent manner. The h-IPE constitutively expressed transforming growth factor beta (TGFbeta) and the receptors, and the T cells exposed to h-IPE greatly expressed Smad transcripts. In addition, TGFbeta2-siRNA transfected h-IPE failed to inhibit activation of responder T cells. Similarly, h-IPE cells in the presence of anti-TGFbeta neutralizing antibodies or recombinant TGFbeta receptor blocking proteins failed to inhibit the T-cell activation. In conclusion, cultured human iris pigment epithelium fully inhibits T cell activation in vitro. Our data support the hypothesis that the ocular resident cells play a critical role in immunosuppression in the eye.

Posterior staphylomas and scleral curvature in highly myopic children and adolescents investigated by ultra-widefield optical coherence tomography.

PURPOSE: To determine the early signs of posterior staphylomas in highly myopic eyes of younger subjects by swept-source ultra-widefield optical coherence tomography (WF-OCT). METHODS: This was an observational case series study. Highly myopic subjects younger than 20 years old who were examined consecutively by prototype WF-OCT were studied. High myopia was defined according to the Ministry of Health and Welfare, Japan classification. A posterior displacement of the sclera and two OCT features indicating the staphyloma edges were used as markers of a staphyloma. RESULTS: Fifty-five eyes of 30 patients with the mean age of 12.3 years, and the mean axial length of 27.9 mm were studied. Seven of the 55 eyes (12.7%) had a posterior displacement of the sclera and were diagnosed as having a staphyloma. Among the two OCT features of the staphyloma edges, a gradual thinning of the choroid toward the staphyloma edge and gradual re-thickening of choroid from the staphyloma edge toward the posterior pole were found in these 7 eyes. However, the other feature of an inward protrusion of the sclera at the staphyloma edge, was obvious in only 2 eyes. The subfoveal choroid and choroid nasal to the optic disc were significantly thinner in eyes with a staphyloma than those without it. CONCLUSIONS: The changes of the choroidal thickness toward the staphyloma edge with the posterior displacement of the sclera were considered an early sign which precedes an inward protrusion of sclera at the staphyloma edge.

[Detection of herpesvirus genome by multiplex polymerase chain reaction (PCR) and real-time PCR in ocular fluids of patients with acute retinal necrosis].

PURPOSE: The human herpesvirus (HHV) family consists of types 1 to 8 (HHV1-8). The purpose of this study was to investigate the detection of HHV DNA, especially HSV1 (herpes simplex virus 1, HHV1), HSV2 (herpes simplex virus 2, HHV2), and VZV (varicella-zoster virus, HHV3) in ocular fluids of patients with acute retinal necrosis(ARN). METHODS: The intraocular genome for HHV1-8 was determined in 19 ocular fluid samples (12 vitreous fluid and 7 aqueous humor samples) taken from ARN patients (n=14). The samples were tested for the presence of virus DNA by two systems of polymerase chain reaction (PCR): the multiplex PCR screening test and real-time quantitative PCR. RESULTS: Multiplex PCR demonstrated VZV (n=16, 84%), HSV1 (n = 1.5%) or HSV2 (n = 2.11%)genomic DNA in all the samples. In real-time PCR, a high copy number of virus DNA was detected. The virus DNA-positive samples contained Epstein-Barr virus (EBV, HHV4) DNA in 9 of 19 samples (47%). No HHV6-8 DNA was detected in the ocular samples, and no virus DNA was detected in the serum samples. CONCLUSIONS: The genome for HHV1-3 was detected in the patients with ARN. All cases contained a high copy number for the virus DNA that indicates viral replication. PCR systems are useful for determing whether virus infections are associated with uveitis.

Immune Privilege and Eye-Derived T-Regulatory Cells.

Certain cellular components of the eye, such as neural retina, are unable to regenerate and replicate after destructive inflammation. Ocular immune privilege provides the eye with immune protection against intraocular inflammation in order to minimize the risk to vision integrity. The eye and immune system use strategies to maintain the ocular immune privilege by regulating the innate and adaptive immune response, which includes immunological ignorance, peripheral tolerance to eye-derived antigens, and intraocular immunosuppressive microenvironment. In this review, we summarize current knowledge regarding the molecular mechanism responsible for the development and maintenance of ocular immune privilege via regulatory T cells (Tregs), which are generated by the anterior chamber-associated immune deviation (ACAID), and ocular resident cells including corneal endothelial (CE) cells, ocular pigment epithelial (PE) cells, and aqueous humor. Furthermore, we examined the therapeutic potential of Tregs generated by RPE cells that express transforming growth factor beta (TGF-ß), cytotoxic T lymphocyte-associated antigen-2 alpha (CTLA-2α), and retinoic acid for autoimmune uveoretinitis and evaluated a new strategy using human RPE-induced Tregs for clinical application in inflammatory ocular disease. We believe that a better understanding of the ocular immune privilege associated with Tregs might offer a new approach with regard to therapeutic interventions for ocular autoimmunity.