Retinal vascular arcade angle as a biomarker for visual improvement after epiretinal membrane surgery.

OBJECTIVES: To investigate the changes in the temporal vascular angles after epiretinal membrane (ERM) surgery and utilize the angles to predict visual outcomes. METHODS: A total of 168 eyes from 84 patients with unilateral ERM who underwent vitrectomy were enrolled from a single institution. The angles of temporal venous (anglevein) and arterial arcades (angleartery) were measured on fundus photographs. The relationships between the angles and the best-corrected visual acuity (BCVA) were explored and multivariable logistic models and receiver operating characteristic (ROC) curves were analyzed to identify the factors that predicted visual outcomes. RESULTS: At baseline, both angleartery and anglevein were narrower in the eyes with ERM than the fellow eyes (p < 0.001 and 0.007) but had no correlation with the baseline BCVA (p = 0.754 and 0.804). Postoperatively, the angleartery and anglevein significantly widened (both p < 0.001) and a greater BCVA improvement was associated with a greater widening of the angleartery (p = 0.029) and anglevein (p = 0.050). Multivariable logistic analyses found a narrower baseline angleartery compared to the fellow eye had a higher chance for BCVA improvement ≧ 2 lines (Odds ratio = 0.97; 95% CI, 0.94-0.99; p = 0.016). ROC curve showed the baseline difference in the angleartery between bilateral eyes predicted BCVA improvement ≧ 2 lines (area under the curve = 0.74; p = 0.035), and a 0.73 sensitivity and 0.80 specificity with a cut-off value of -27.19 degrees. CONCLUSIONS: The retinal vascular angles widened after ERM surgery and the fundus photograph-derived angles may serve as a highly-accessible biomarker to predict postoperative visual outcomes.

Oncologist-led germline genetic testing for uveal melanoma.

PURPOSE: To report the genotype and phenotype of a cohort of unselected uveal melanoma (UM) patients who had germline multi-gene panel genetic testing, including the BAP1 gene, from a large multi-ethnic cancer centre. We describe the central role of the medical genetics clinic in collaboration with oncologists in a mainstreaming model to facilitate genetic testing, counselling and streamlining of patients with hereditary cancer predisposition. METHODS: A retrospective chart review of clinical and genetic findings of unselected UM patients who had germline genetic testing between December 2019 and October 2021 was conducted. Extracted DNA from peripheral blood samples were analyzed with a multi-gene panel that included at least six genes associated with hereditary melanoma. The correlation between the genotype and the phenotype of the cohort was evaluated. Statistical analysis comprised descriptive and comparative statistics with significance assigned at p < .05. The genetics clinic streamlined patients among the relevant oncology clinics for cancer screening in germline BAP1 positive individuals. RESULTS: In unselected UM patients, 3.5% (4/114) tested positive for a BAP1 pathogenic variant. Germline BAP1 status was associated with a family history of mesothelioma (p = .0015) and metastatic disease (p = .017). There were no other significant associations between the patient- or tumour-related characteristics and germline BAP1 results. CONCLUSION: A germline BAP1 mutation was detected in 3.5% of unselected UM patients. The oncologist-initiated and genetics-led mainstreaming model is a straightforward process and can be utilized for offering genetic testing to all UM patients.

Cytogenetic Abnormalities for Predicting the Risk of Metastases in Choroidal and Ciliary Body Melanoma.

Purpose: Choroidal melanoma (CM) and ciliary body melanoma (CBM) are the two most common subtypes of uveal melanoma. Starting from the observation that CBM tends to have a higher metastatic potential than CM, we hypothesized that specific cytogenetic abnormalities could be associated with tumor location - reflecting distinct genetic signatures that would drive the risk of distant spread. Methods: Chromosomal alterations were investigated by molecular cytogenetic techniques in 217 and 97 patients with CM and CBM, respectively. Cox proportional hazards regression analysis was used to identify the independent predictors of distant metastasis. Results: Patients with CBM had larger tumor sizes (P < 0.001), higher disease stages (P < 0.001), and more frequently showed distant metastasis (P = 0.002) than those with CM. On analyzing the entire study cohort, we found that specific chromosomal alterations - including chromosome 8p loss (P < 0.001), 1p loss (P < 0.001), and monosomy 3 (P < 0.005) - were independent predictors of distant metastasis. Based on a decision-tree learning algorithm, we identified three specific subgroups of patients with uveal melanoma at high risk of distant spread. Monosomy 3 occurred significantly more frequently in patients with T3 CBM tumors. Conclusions: Specific cytogenetic abnormalities - including chromosome 8p loss, 1p loss, and monosomy 3 - are independent risk factors for distant metastasis in uveal melanoma. Larger tumor size at presentation and monosomy 3 contribute to a higher metastatic risk in patients with CBM.

Epidemiology, Treatment, and Outcomes of Juvenile Idiopathic Arthritis-Associated Uveitis: A Multi-Institutional Study in Taiwan.

PURPOSE: To assess the epidemiology, treatment, and outcomes of juvenile idiopathic arthritis (JIA)-associated uveitis (JIA-U) in Taiwan. METHODS: Retrospective, multicenter database. RESULTS: Totally, 44 (6.1%) of the 722 JIA patients had uveitis. The mean ages of JIA and JIA-U diagnosis were 10.7 and 11.1 years, respectively. JIA-U patients had more antinuclear antibody presence. Among JIA-U patients, 25 (56.8%) were male, 11 (25.0%) experienced any ocular complication, and 8 (18.2%) received ocular surgery. Inactivity lasting ≥6 months was achieved in 17 (38.6%) patients; however, 11 (25.0%) of those experienced reactivation with a mean of 624.7 days after achieving inactivity. Female had more ocular complications and surgeries. CONCLUSION: Late age at JIA-U diagnosis and male predominance were distinctive in Taiwan. For patients with inactivity lasting ≥ 6 months was achieved, they still required close follow-up due to the high reactivation rate within 2 years. Female had poorer ocular outcomes.

Seven-year follow-up of a pediatric patient with combined hamartoma of retina and retinal pigment epithelium complicating with preretinal neovascularization and vitreous hemorrhage treated with intravitreal injections of bevacizumab.

We report a case of successful management of intravitreal injections of anti-vascular endothelial growth factor antibody bevacizumab in two unusual complications, preretinal neovascularization and vitreous hemorrhage, secondary to a combined hamartoma of the retina and retinal pigment epithelium (CHRRPE). A male pediatric patient suffered from decreased vision in the right eye at 5-year-old. His ophthalmologic examination revealed a CHRRPE involving the superior area of the optic disc and macula in the right eye. The patient's family history and neurological examinations of tuberous sclerosis were absent. While no lesion growth was observed over time, preretinal vascularization and recurrent nonclearing hemorrhage occurred 2 years after the initial presentation. The patient was successfully managed with two intravitreal injections of bevacizumab. No recurrences of vitreous hemorrhage were observed at a 7-year post-treatment follow-up. Intravitreal injections of bevacizumab were safe and effective in the management of uncommon complications of preretinal neovascularization and vitreous hemorrhage of CHRRPE in a pediatric patient in long-term follow-up.

Congenital Stationary Night Blindness: Clinical and Genetic Features.

Congenital stationary night blindness (CSNB) is an inherited retinal disease (IRD) that causes night blindness in childhood with heterogeneous genetic, electrophysical, and clinical characteristics. The development of sequencing technologies and gene therapy have increased the ease and urgency of diagnosing IRDs. This study describes seven Taiwanese patients from six unrelated families examined at a tertiary referral center, diagnosed with CSNB, and confirmed by genetic testing. Complete ophthalmic exams included best corrected visual acuity, retinal imaging, and an electroretinogram. The effects of identified novel variants were predicted using clinical details, protein prediction tools, and conservation scores. One patient had an autosomal dominant CSNB with a RHO variant; five patients had complete CSNB with variants in GRM6, TRPM1, and NYX; and one patient had incomplete CSNB with variants in CACNA1F. The patients had Riggs and Schubert-Bornschein types of CSNB with autosomal dominant, autosomal recessive, and X-linked inheritance patterns. This is the first report of CSNB patients in Taiwan with confirmed genetic testing, providing novel perspectives on molecular etiology and genotype-phenotype correlation of CSNB. Particularly, variants in TRPM1, NYX, and CACNA1F in our patient cohort have not previously been described, although their clinical significance needs further study. Additional study is needed for the genotype-phenotype correlation of different mutations causing CSNB. In addition to genetic etiology, the future of gene therapy for CSNB patients is reviewed and discussed.

Infection Sources and Klebsiella pneumoniae Antibiotic Susceptibilities in Endogenous Klebsiella Endophthalmitis.

Endogenous endophthalmitis is an uncommon intraocular infection with potentially devastating consequences on vision. Klebsiella pneumoniae is highly prevalent in East Asian countries, with an increasing incidence recently worldwide. This retrospective study investigates infection sources and antibiotic susceptibilities of K. pneumoniae in patients with endogenous K. pneumoniae endophthalmitis (EKE) in Northern Taiwan. One hundred and fifty-seven patients with EKE were reviewed between January 1996 and April 2019. Pyogenic liver abscess (120/157, 76.4%) was the most common infection source, followed by pneumonia (13, 8.3%), urinary tract infection (7, 4.5%), and intravenous drug use (4, 2.5%). Bilateral involvement was identified in 12.1% (19/157) of patients, especially in patients with pyogenic liver abscess (16/120, 13.3%), pneumonia (2/13, 15.4%), and urinary tract infection (1/7, 14.3%). The antibiotic susceptibility rates were 98.1%, 92.5%, 97.5%, 96.8%, 100%, 99.3%, and 100% for amikacin, cefuroxime, ceftazidime, ceftriaxone, carbapenems, ciprofloxacin, and levofloxacin, respectively. Four extended-spectrum ß-lactamase-producing multidrug-resistant (MDR) K. pneumoniae isolates were identified. In conclusion, pyogenic liver abscess was the major infection source in EKE. In addition, K. pneumoniae was still highly susceptible to ceftazidime and amikacin, and the MDR K. pneumoniae isolates were not common in EKE.

Endogenous Fungal Endophthalmitis: Causative Organisms, Treatments, and Visual Outcomes.

Endogenous fungal endophthalmitis (EFE) is a vision-threatening intraocular infection and a rare complication of fungemia. Early diagnosis and prompt aggressive treatment are crucial to avoid vision loss. We retrospectively reviewed the data of 37 patients (49 eyes) with EFE who were treated at a tertiary referral hospital from January 2000 to April 2019. The most common risk factor was diabetes (24 patients; 65%), followed by recent hospitalization, urinary tract disease, liver disease, and immunosuppressive therapy. Two or more risk factors were detected in 24 patients (65%), and yeasts (29 patients; 78%) were more commonly detected than mold (8 patients; 22%). The most common fungal isolates were Candida spp. (78%), especially Candida albicans (70%). Moreover, 24 eyes in 21 patients underwent vitrectomy, and 2 eyes underwent evisceration. Retinal detachment (RD) occurred in 17 eyes (35%) in 14 patients, and eyes without RD exhibited significantly superior visual outcomes (p = 0.001). A comparison of the initial VA between the better (20/200 or better) and worse groups (worse than 20/200) revealed that better initial VA was related to a superior visual outcome (p = 0.003). Therefore, to achieve superior visual outcomes, early diagnosis and prompt treatment are necessary for patients with EFE.

Retinoblastoma in Taiwan: survival and clinical characteristics.

PURPOSE: To figure out the impact of national health insurance program and treatment modalities on the clinical outcomes of patients with retinoblastoma. STUDY DESIGN: Retrospective cohort study. METHODS: Enrolled patients were classified into three groups according to the time period in which their initial diagnosis was performed: patients diagnosed before 1995 (group 1), patients diagnosed in the time period 1995-2010 (group 2), patients diagnosed after 2010 (group 3). Comparison was made of clinical features including presenting signs, tumor spreading, and treatment modes. Survival and globe salvage rates were analyzed within each group. RESULTS: There were 157 patients (202 eyes) enrolled from 1978 to 2015. The overall mortality rate was 24.2%. The overall 5-year survival rate was 63.4%, 73.8%, 89.1% in the three time periods respectively (P = 0.007). The 5-year survival improved continuously in both unilateral and bilateral disease (P = 0.057; P = 0.015). Patients without extraocular spreading or diagnosed before 2 years of age had a better 5- year survival of 97.4% and 81.1% respectively. The globe salvage rate improved from 8.2%, 14.5%, to 35.1% (P < 0.001). The globe salvage rate was 46.9% in patients who received ophthalmic artery chemosurgery (OAC) and 6.4% in patients not received OAC. CONCLUSIONS: Improvement of survival and globe salvage rate was observed over time periods. National health insurance program has made medical care easily accessible to the public, leading to earlier diagnosis and treatment. Different treatment modes could achieve a better clinical outcome; among the new treatment modalities, OAC played an important role.

Enterococcus faecalis Endophthalmitis: Clinical Settings, Antibiotic Susceptibility, and Management Outcomes.

Enterococcus faecalis is known to cause severe acute endophthalmitis and often leads to poor visual outcomes in most ophthalmic infections. This retrospective study is to report the clinical settings, antimicrobial susceptibility patterns, and visual outcome of E. faecalis endophthalmitis at a tertiary referral institution in Taoyuan, Taiwan. E. faecalis endophthalmitis was diagnosed in 37 eyes of 37 patients. Post-cataract surgery was the most common cause (n = 27, 73%), followed by bleb-associated (n = 3, 8%), endogenous (n = 2, 5%), corneal ulcer-related (n = 2, 5%), post-vitrectomy (n = 1, 3%), post-pterygium excision (n = 1, 3%), and trauma (n = 1, 3%). Visual acuities upon presentation ranged from counting fingers to no light perception. Pars plana vitrectomy with intravitreal antibiotics were performed in 23 eyes (76%) as primary or secondary treatment. All isolates (37/37, 100%) were sensitive to vancomycin, penicillin, ampicillin, and teicoplanin. Six of 22 eyes (27%) were resistant to high-level gentamicin (minimum inhibitory concentration > 500 mg/L). Final visual acuities were better than 20/400 in 11 eyes (30%), 5/200 to hand motions in 4 eyes (11%), and light perception to no light perception in 22 eyes (59%). Three eyes were treated with evisceration. Compared with non-cataract subgroups, the post-cataract subgroup showed a significant difference of better visual prognosis (p = 0.016).

RATES AND RISK FACTORS FOR RECURRENCE OF RETINOPATHY OF PREMATURITY AFTER LASER OR INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR MONOTHERAPY.

PURPOSE: To determine the rates and risk factors of recurrent retinopathy of prematurity (ROP) treated by laser photocoagulation, intravitreal bevacizumab (IVB) monotherapy, or intravitreal ranibizumab (IVR) monotherapy. METHODS: In this retrospective cohort study, consecutive infants with Type 1 ROP who received laser, IVB, or IVR treatments were followed for at least 75 weeks of postmenstrual age. Data analysis was performed between March 2010 and February 2017 in Chang Gung Memorial Hospital, Linkou, Taiwan. RESULTS: A total of 176 infants (340 eyes) were included in this study. The mean follow-up was 197.3 ± 110 weeks. All of the baseline demographic and ROP characteristics among the laser, IVB, and IVR groups were similar. The overall recurrence rate after treatment was 44 of 340 eyes (12.9%). The IVB group had a recurrence rate of 10.0%, followed by the laser group (18.0%) and the IVR group (20.8%); however, these rates were not significantly different (P = 0.0528). Compared with the laser group, the IVB and IVR groups exhibited recurrence at later ages (43.4 ± 3.5 weeks for the IVB group, 42.3 ± 2.0 weeks for the IVR group, and 39.5 ± 2.8 weeks for the laser group; P = 0.0058). The mean interval of recurrence from initial treatment in the laser group was 3.6 ± 1.4 weeks compared with 8.8 ± 3.9 weeks and 8.3 ± 1.6 weeks in the IVB and IVR groups, respectively (P = 0.0001). Overall, the independent risk factors of recurrence included an early postmenstrual age at initial treatment (P = 0.0160), Zone I (P = 0.0007), low Apgar score (P = 0.0297), and multiple births (P = 0.0285). There was no significant difference in progression to retinal detachment among the three groups (laser: 3/61, 4.9%; IVB: 2/231, 0.9%;and IVR: 1/48, 2.1%; P = 0.2701). CONCLUSION: Laser, IVR, and IVB are effective for Type 1 ROP. Retinopathy of prematurity recurrence requiring re-treatment was encountered as late as 50 weeks of postmenstrual age after IVB or IVR but earlier after laser. Longer follow-up for infants treated with anti-vascular endothelial growth factor is needed, especially in patients with significant risk factors such as an early postmenstrual age at initial treatment, Zone I ROP, low Apgar score, and multiple births.

FLUORESCEIN ANGIOGRAPHY FINDINGS IN UNILATERAL PERSISTENT FETAL VASCULATURE.

OBJECTIVE: This study aims to examine retinal vascular findings for affected eyes and contralateral eyes as well in typical cases of unilateral persistent fetal vasculature. METHODS: We retrospectively reviewed all patients evaluated at Chang Gung Memorial Hospital, Linkou, for unilateral persistent fetal vasculature between January 2008 and July 2017. All patients underwent fluorescein angiography (FA) examination under general anesthesia. FA was performed using RetCam 3 (Clarity Medical Systems, Inc, Pleasanton, CA). RESULTS: Ten patients (eight male and two female) were identified as having adequate clinical data for the final analysis. The mean age at diagnosis was 13.7 ± 17.2 months (range 1-58). The mean axial length was shorter in the affected eyes as compared to the fellow eyes (17.27 ± 2.8 vs. 20.2 ± 1.7 mm; P = 0.024). In the affected eyes, nine cases (90.0%) showed a concomitant retrolental stalk, avascular peripheral retina, regional capillary dropout, and absence of foveal avascular zone. Hyperfluorescent stalk was seen in seven cases (70.0%). Four eyes (40.0%) showed leaking vessels. Terminal supernumerary branching was seen in two cases (20.0%). Popcorn hyperfluorescence was noted in one case (10.0%). In the fellow eyes, peripheral avascular zone was noted in nine eyes (90.0%), of which six (60.0%) had peripheral zones greater than two-disk diameters. Seven eyes (70.0%) presented with regional capillary dropout and abnormal choroidal filling. Three eyes (30.0%) had abnormal vessel straightening. Aberrant circumferential vessels and leaking spots were seen in two eyes (20.0%). Regional dilation of disk vessels, peripheral vessel dilation, and terminal bulbing were noted in one eye (10.0%). The mean best-corrected visual acuity of the fellow eyes was 20/39 (0.29 in logarithm of the minimum angle of resolution). CONCLUSION: Retinal vascular abnormalities in the affected eyes and fundoscopically normal fellow eyes of unilateral persistent fetal vasculature patients were found in 100% and 90.0% of patients, respectively. Fellow eyes had some subtle abnormalities that were only revealed through FA. These unilateral persistent fetal vasculature cases were still bilaterally affected.

Visual and Anatomical Outcomes With Vitrectomy in Posterior or Combined Persistent Fetal Vasculature in an Asian Population.

BACKGROUND AND OBJECTIVE: To investigate clinical features and surgical outcomes of vitrectomy in posterior or combined persistent fetal vasculature (PFV) in an Asian pediatric population. PATIENTS AND METHODS: This study was a retrospective, noncomparative, interventional case series relating the surgical outcome of PFV. Eyes that underwent pars plicata vitrectomy and/or lensectomy for posterior or combined PFV between 2006 and 2015 were included. The main outcome measures were the anatomic and functional results as well as the complications after the vitrectomy with or without lensectomy. RESULTS: A total of 25 eyes of 18 patients younger than 8 years of age were included in the study. The mean age of the patients receiving first pars plicata vitrectomy and/or lensectomy was 15.2 months ± 21.7 months (range: 1 month to 83 months). Postoperatively, successful anatomic correction in the posterior segment was observed in 20 eyes (80%). In addition, 19 of the 25 eyes (76%) had visual acuity (VA) better than 20/4000, and the mean logMAR VA of these 19 eyes was 1.74 (range: 0.48 to 2.30). The mean change of axial length of the eyes receiving surgery was 0.7 mm ± 1.4 mm (range: -1.0 mm to 2.4 mm; P = .18). None of the patients ended up with phthisis or glaucoma. CONCLUSIONS: This study suggests that vitrectomy and/or lensectomy in patients with posterior or combined PFV with macular involvement may result in an acceptable anatomical outcome; however, the functional outcome remained poor despite surgical intervention in these patients. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:377-384.].

Prognostic Factors and Visual Outcomes of Pyogenic Liver Abscess-Related Endogenous Klebsiella pneumoniae Endophthalmitis: A 20-year retrospective review.

Endogenous K. pneumoniae endophthalmitis (EKE) has a higher incidence among East Asians, and the most common infectious source of EKE is pyogenic liver abscess (PLA). We investigate the risk factors for poor visual outcomes in patients with PLA-related EKE. The retrospective medical records of 104 patients (120 eyes) diagnosed with PLA-related EKE between 1996 and 2015. In univariate logistic regression analysis, the risk factors for poor visual outcomes were initial visual acuity (VA) worse than counting fingers (CF) (p < 0.001), eye pain (p = 0.013), hypopyon (p = 0.003), ocular hypertension (p = 0.003), positive intraocular fluids cultures (p < 0.001), subretinal abscess (p = 0.025), unilateral involvement (p = 0.017), delayed ophthalmologic visit (p = 0.022), initially presented with ocular symptoms ahead of systemic symptoms (p < 0.001), and corneal edema (p < 0.001). Intravitreal dexamethasone reduced the requirement of enucleation or evisceration (p = 0.01). The multivariate logistic regression revealed that poor initial VA worse than CF (p = 0.004) and initially presented with ocular symptoms ahead of systemic symptoms (p = 0.007) were the significant independent factors for poor visual outcomes. Early diagnosis and prompt treatment may salvage useful vision in some eyes.

Histopathologic findings after selective ophthalmic arterial injection of melphalan for retinoblastoma.

PURPOSE: The aim is to describe histopathologic observations in eyes enucleated after selective ophthalmic arterial injection (SOAI) of melphalan for retinoblastoma (RB). STUDY DESIGN: This is retrospective clinical study. PATIENTS AND METHODS: Histopathologic analysis of 14 eyes (13 patients) from May 2008 through January 2015 at Chang Gung Memorial Hospital. RESULTS: The eyes after SOAI were enucleated due to tumor viability (n = 7, 2 with vitreous hemorrhage), neovascular glaucoma (n = 4), lens drop to vitreous with total hyphema and elevated intraocular pressure (n = 1), retinal detachment (RD) progressed (n = 1), and persistent RD with phthisis change (n = 1). Almost all of the eyes showed vitreous seeding (n = 11 eyes) before treatment. After the treatment of SOAI, the histopathological examination revealed complete regression in four eyes with one was clinically diagnosed as viable tumor and progression, one with RD progression, and two as neovascular glaucoma. Six eyes showed invasion into the optic nerves, reaching the lamina cribrosa in five eyes, and six eyes with invasion into the choroid were observed. All of the cases with lamina cribrosa involvement showed tumor progression before enucleation, four cases with lamina cribrosa involvement expired later. CONCLUSION: Although some cases of RB can be controlled effectively with SOAI, but for refractory cases after SOAI, earlier decision of enucleation may be needed.

Interferon-α-induced retinopathy in chronic hepatitis C treatment: summary, considerations, and recommendations.

Interferons are cytokines that regulate the host's response to viral infection, particularly in the setting of the immunologic response to the hepatitis C virus (HCV). While the virus has the ability to evade the host's innate and specific immunity, exogenous interferon-α with combined ribavirin, treatments have been found to achieve a significant sustained viral response in subgroups of patients with chronic HCV. One of the major side effects of interferon-α is an ocular retinopathy characterized by flame-shaped hemorrhages and cotton wool spots visualized on funduscopic examination. There have been documented cases of more severe side effects including optic nerve and retinal artery damage; however, these instances are the minority. We sought to investigate the literature surrounding interferon-induced retinopathy, clinically correlate our findings with two recent cases, and provide recommendations for practitioners who continue to manage chronic HCV patients using interferon-α with combined ribavirin treatments.