Un Chul Park

Ahmed glaucoma valve implantation for neovascular glaucoma after vitrectomy for proliferative diabetic retinopathy.

PurposeTo evaluate the safety and efficacy of Ahmed Glaucoma Valve implantation (AGVI) for the management of neovascular glaucoma (NVG) associated with proliferative diabetic retinopathy (PDR) in the vitrectomized eyes. Patients and MethodsWe reviewed the medical records of patients with NVG associated with PDR who underwent AGVI for intraocular pressure (IOP) control and compared the surgical outcome according to vitrectomy history. The main outcome measures were: postoperative IOP control, visual acuity, and complications. Success was defined as an IOP of ⩽21 mm Hg and ≥6 mm Hg, without further glaucoma surgery or loss of light perception and devastating complications. ResultsA total of 73 patients (73 eyes) were included: 42 patients with vitrectomy history before AGVI (vitrectomized group) and 31 patients without vitrectomy history (nonvitrectomized group). The cumulative probabilities of success after AGVI were 89.9% and 83.8% after 1 year, 74.8% and 74.7% after 2 years, and 62.5% and 68.5% after 3 years for the vitrectomized group and the nonvitrectomized group, respectively (P=0.9309). Cox proportional hazards regression showed the intraocular silicone oil tamponade as a risk factor for the surgical failure (odds ratio=4.543, P=0.047). Final visual acuity improved or stabilized in 33 patients (78.6%) in the vitrectomized group and 18 patients (58.1%) in the nonvitrectomized group. Complications were comparable between the groups, but surgical interventions were needed for 5 patients (11.9%) in the vitrectomized group. ConclusionDespite some complications that necessitate surgical intervention, the AGVI is a safe and effective procedure that enables successful IOP control and vision preservation in patients with NVG associated with vitrectomy for the PDR.

Genetic factors associated with response to intravitreal ranibizumab in Korean patients with neovascular age-related macular degeneration.

Purpose: To investigate the association between genetic risk variants for age-related macular degeneration (AMD) and response to intravitreal ranibizumab in Korean patients with neovascular AMD. Methods: This prospective study included 273 treatment-naive patients (273 eyes) who underwent 5 monthly injections (Months 0, 1, 2, 3, and 4) of intravitreal ranibizumab for neovascular AMD. Patients were genotyped for 23 single-nucleotide polymorphisms within 12 AMD-relevant genes. For each polymorphism, genotypic association with good response at Month 5, predetermined as visual improvement of ≥8 Early Treatment Diabetic Retinopathy Study letters from baseline, was investigated with logistic regression analysis adjusted for age, gender, smoking, baseline Early Treatment Diabetic Retinopathy Study letter, central retinal thickness, lesion area, and type of choroidal neovascularization. Results: At Month 5, visual acuity improved by 9.1 ± 17.6 letters from baseline, and 136 patients (49.8%) were classified as good responders. In logistic regression, no tested polymorphism showed statistically significant association with favorable visual outcome at Month 5. When unadjusted for multiple tests, AA genotype for VEGF rs699947 had an increased chance of good response compared with other genotypes (odds ratio, 3.61; 95% confidence interval, 1.42–9.18; P = 0.0071). Conclusion: In this Korean neovascular AMD cohort, there was no statistically significant effect of genotype on early visual outcome after ranibizumab treatment.

Long-term outcome of intravitreal triamcinolone acetonide injection for the treatment of uveitis attacks in Behçet disease.

Abstract Purpose: To evaluate the long-term efficacy and safety of intravitreal triamcinolone acetonide (IVTA) injection for posterior segment inflammation in Behçet disease (BD) patients. Methods: The authors reviewed the medical records of BD patients who underwent IVTA injection (4 mg/0.1 mL) for posterior uveitis attack unresponsive to systemic immunosuppression and were followed up for more than 24 months. Results: Forty-nine patients (49 eyes) were included. Mean best-corrected visual acuity improved from 0.89 logMAR units to 0.70, 0.64 at 12, 24 months, respectively. Complete inflammation control was achieved in 87.0% of patients, but 60.0% of them experienced relapse within 12 months. For phakic eyes, cumulative probabilities for cataract surgery were 13.8%, 48.9%, and 60.2% at 12, 24, and 36 months, respectively. Intraocular pressure elevation exceeding 21 mmHg was noted in 40.8%. Conclusions: In Behçet uveitis attack that is unresponsive or intolerant to systemic medications, IVTA injection is an effective therapeutic option, although ocular complications could limit its efficacy and repeatability.

Cytomegalovirus Endotheliitis after Fluocinolone Acetonide (Retisert) Implant in a Patient with Behçet Uveitis

Purpose: To report a case of cytomegalovirus (CMV) endotheliitis after insertion of an intravitreal fluocinolone acetonide (Retisert) implant. Design: Interventional case report. Methods: Retrospective chart review. Results: A 40-year-old man received a Retisert implant in the left eye for recurrent Behçet uveitis. Although inflammation became quiescent within a month, corneal edema developed 4 months after insertion. Polymerase chain reaction analysis for aqueous humor detected 3.9 × 104 copies/mL of CMV DNA. After treatment with oral valganciclovir, CMV DNA nearly disappeared but visual outcome was poor due to corneal decompensation resulting from severe endothelial cell loss. Conclusions: After Retisert implant, clinicians should be attentive to the potential risk of CMV endotheliitis.

Generation of retinal pigment epithelial cells from human embryonic stem cell-derived spherical neural masses☆

Dysfunction and loss of retinal pigment epithelium (RPE) are major pathologic changes observed in various retinal degenerative diseases such as aged-related macular degeneration. RPE generated from human pluripotent stem cells can be a good candidate for RPE replacement therapy. Here, we show the differentiation of human embryonic stem cells (hESCs) toward RPE with the generation of spherical neural masses (SNMs), which are pure masses of hESCs-derived neural precursors. During the early passaging of SNMs, cystic structures arising from opened neural tube-like structures showed pigmented epithelial morphology. These pigmented cells were differentiated into functional RPE by neuroectodermal induction and mechanical purification. Most of the differentiated cells showed typical RPE morphologies, such as a polygonal-shaped epithelial monolayer, and transmission electron microscopy revealed apical microvilli, pigment granules, and tight junctions. These cells also expressed molecular markers of RPE, including Mitf, ZO-1, RPE65, CRALBP, and bestrophin. The generated RPE also showed phagocytosis of isolated bovine photoreceptor outer segment and secreting pigment epithelium-derived factor and vascular endothelial growth factor. Functional RPE could be generated from SNM in our method. Because SNMs have several advantages, including the capability of expansion for long periods without loss of differentiation capability, easy storage and thawing, and no need for feeder cells, our method for RPE differentiation may be used as an efficient strategy for generating functional RPE cells for retinal regeneration therapy.

Subretinal transplantation of putative retinal pigment epithelial cells derived from human embryonic stem cells in rat retinal degeneration model

Objective To differentiate the human embryonic stem cells (hESCs) into the retinal pigment epithelium (RPE) in the defined culture condition and determine its therapeutic potential for the treatment of retinal degenerative diseases. Methods The embryoid bodies were formed from hESCs and attached on the matrigel coated culture dishes. The neural structures consisting neural precursors were selected and expanded to form rosette structures. The mechanically isolated neural rosettes were differentiated into pigmented cells in the media comprised of N2 and B27. Expression profiles of markers related to RPE development were analyzed by reverse transcription-polymerase chain reaction and immunostaining. Dissociated putative RPE cells (105 cells/5 µL) were transplanted into the subretinal space of rat retinal degeneration model induced by intravenous sodium iodate injection. Animals were sacrificed at 1, 2, and 4 weeks after transplantation, and immnohistochemistry study was performed to verify the survival of the transplanted cells. Results The putative RPE cells derived from hESC showed characteristics of the human RPE cells morphologically and expressed molecular markers and associated with RPE fate. Grafted RPE cells were found to survive in the subretinal space up to 4 weeks after transplantation, and the expression of RPE markers was confirmed with immunohistochemistry. Conclusion Transplanted RPE cells derived from hESC in the defined culture condition successfully survived and migrated within subretinal space of rat retinal degeneration model. These results support the feasibility of the hESC derived RPE cells for cell-based therapies for retinal degenerative disease.

Immunopathogenesis of Ocular Behçet’s Disease

Behçets disease (BD) is a chronic recurrent systemic inflammatory disorder of unknown etiology characterized by oral and genital ulcerations, skin lesions, and uveitis. The ocular involvement of BD, or Behçets uveitis (BU), is characterized by panuveitis or posterior uveitis with occlusive retinal vasculitis and tends to be more recurrent and sight threatening than other endogenous autoimmune uveitides, despite aggressive immunosuppression. Although pathogenesis of BD is unclear, researches have revealed that immunological aberrations may be the cornerstone of BD development. General hypothesis of BD pathogenesis is that inflammatory response is initiated by infectious agents or autoantigens in patients with predisposing genetic factors and perpetuated by both innate and acquired immunity. In addition, a network of immune mediators plays a substantial role in the inflammatory cascade. Recently, we found that the immunopathogenesis of BU is distinct from other autoimmune uveitides regarding intraocular effector cell profiles, maturation markers of dendritic cells, and the cytokine/chemokine environment. In addition, accumulating evidence indicates the involvement of Th17 cells in BD and BU. Recent studies on genetics and biologics therapies in refractory BU also support the immunological association with the pathogenesis of BU. In this review, we provide an overview of novel findings regarding the immunopathogenesis of BU.

Long-term Change of Subfoveal Choroidal Thickness in Behçet’s Disease Patients with Posterior Uveitis

ABSTRACT Purpose: To evaluate long-term changes of subfoveal choroidal thickness (SCT) in Behçet’s disease (BD) patients with posterior uveitis. Methods: Changes in SCT measured with enhanced depth imaging optical coherence tomography during quiescent phase were assessed during >24 months in 63 BD patients and control group. Results: Baseline characteristics showed no difference, but the BD group showed poorer visual acuity (p = 0.013) and smaller SCT (p = 0.006) at final examination. Mean SCT in the BD group decreased from 291.0 to 268.1 μm (p<0.001) during the mean period of 38.5 months. Mean change rate of SCT in the BD group was greater than controls (–7.2 vs 2.0 μm/year; p<0.001) and was associated with longer active inflammation (p<0.001). Patients with longer disease duration showed smaller baseline SCT (p = 0.03). Conclusions: In BD patients, choroidal thickness decreased over time, which was associated with length of active inflammation. It suggests intraocular inflammation in BD affects the choroid as well as the retina.

Inter-observer Variability in Scoring Ultra-wide-field Fluorescein Angiography in Patients with Behçet Retinal Vasculitis.

ABSTRACT Purpose: To test inter-observer agreement in applying the scoring system of the Angiography Scoring of Uveitis Working Group (ASUWG) to ultra-wide-field fluorescein angiograms (UWFA) obtained from patients with Behçet retinal vasculitis. Methods: Both standard FA and UWFA images were obtained from 21 patients with retinal vasculitis associated with Behçet disease. Three graders independently graded 21 series of standard FA and 21 series of UWFA images. Spearman rank correlation and the intra-class correlation coefficient (ICC) were used to analyze the correlations. Results: Total scores of all angiographic signs observed in both UWFA and standard FA images were significantly correlated between each pair of graders and among the three graders (ICC of standard FA = 0.874, p<0.001; ICC of UWFA = 0.928, p<0.001). Conclusions: The ASUWG scoring system is a reliable method of scoring UWFA images with regard to judging the activity of retinal vasculitis in ocular Behçet disease.

Choroidal vascularity changes in idiopathic central serous chorioretinopathy after half-fluence photodynamic therapy

Purpose This study evaluated changes in choroidal vascularity after half-fluence photodynamic therapy (HF-PDT) in patients with central serous chorioretinopathy (CSC) using swept-source optical coherence tomography (SS-OCT) en face imaging. Methods This retrospective comparative case series included 50 eyes of 25 patients with unilateral CSC who underwent HF-PDT and 50 age-and sex-matched normal healthy control eyes. En face SS-OCT images of the choriocapillaris, Sattler’s layer, and Haller’s layer were converted into binary images. The vascular proportions were defined as the percentage of the area of vascular lumen against the area of the 3.0-mm-diameter circular area. The main outcome measures were the vascular proportions before HF-PDT and at 6 weeks, 6 months, and 12 months after HF-PDT. Results At baseline, the vascular proportions in the CSC eyes were significantly greater than those in the control eyes in all layers (choriocapillaris: 51.8% ± 15.5% vs. 41.3 ± 18.7%, P = 0.018; Sattler’s: 58.6% ± 13.4% vs. 49.7% ± 15.7%, P = 0.017; Haller’s: 65.3% ± 15.3% vs. 53.0% ± 13.4%, P = 0.001). In the CSC eyes, the vascular proportion in the choriocapillaris significantly decreased at 6 weeks (36.6% ± 16.9%, P < 0.001), 6 months (34.0% ± 12.3%, P < 0.001), and 12 months (34.8% ± 17.6%, P < 0.001) after HF-PDT compared with baseline. The vascular proportions in Sattler’s and Haller’s layers did not show a significant decrease at 6 weeks (Sattler’s: 49.7% ± 17.3%, P = 0.052 and Haller’s: 58.3% ± 12.9%, P = 0.558) but decreased significantly at 6 months (Sattler’s: 48.9% ± 12.4%, P < 0.001 and Haller’s: 57.7% ± 15.7%, P = 0.027) and 12 months after HF-PDT from the baseline values (Sattler’s: 45.8% ± 10.4%, P < 0.001 and Haller’s: 56.8% ± 15.7%, P < 0.001). Conclusion After HF-PDT, the choriocapillaris showed the earliest decrease in vascular proportion of en face images, Sattler’s and Haller’s layers showed later decreases. The temporal differences in the response of each layer may reflect the pathophysiology of CSC and the therapeutic mechanism of HF-PDT.