Decreased peri-parafoveal RPE, EZ and ELM intensity: A novel predictive biomarker for hydroxychloroquine retinal toxicity.

PURPOSE: To evaluate the reflectivities of the retinal pigment epithelium (RPE), ellipsoid zone (EZ), and external limiting membrane (ELM) in the central fovea, perifoveal, and parafoveal regions with Optical Coherence Tomography (OCT) and the change in choroid vascular index (CVI) in patients using hydroxychloroquine (HCQ). METHODS: Sixty-one patients underwent HCQ treatment; age and sex-matched 44 control group subjects were included in the study. The RPE, EZ, and ELM reflectivities were measured with the ImageJ program at 5 points, and CVI was calculated. RESULTS: RPE, EZ, and ELM reflectivities in the central fovea were higher in the HCQ group than in the control group (p < 0.001, p = 0.013, p = 0.022). In the HCQ group, there was a decrease in RPE reflectivities in the temporal, nasal parafovea, and nasal perifovea (p = 0.001, p = 0.03, p = < 0.001). EZ and ELM reflectivity in the nasal parafovea and nasal perifovea was lower in the patient group than in the control group (p = 0.007, p = 0.005, p = 0.009, p = 0.001). In the HCQ group, all absolute para and perifoveal reflectivities relative to the fovea decreased significantly more than in the control group (p < 0.05). CONCLUSION: In patients who underwent HCQ treatment, there is a decrease in the reflectivities of the para and perifoveal RPE, EZ, and ELM compared to the fovea. This decrease is more pronounced than the decrease in reflectivity in the para and perifoveal regions compared to the fovea in people who do not use HCQ. This situation can be considered as a sign of toxicity that is a precursor to overt maculopathy.

Quantification of retinal vein and artery trajectories using second-order polynomial equation in eyes with vitreomacular traction.

BACKGROUNDS: To measure the degree of curvature of the retinal artery trajectory (RAT) and retinal vein trajectory (RVT) in the eyes of patients with vitreomacular traction (VMT) and compare them with their healthy fellow eyes. METHODS: This was a retrospective, cross-sectional, case-control study of 58 eyes of 29 patients with unilateral VMT. The participants were divided into two groups. Group 1 VMT was defined as having only morphological changes, while group 2 VMT was defined as morphological changes accompanied by the presence of a cyst or hole to quantify the severity of the disease. The RATs and RVTs were assessed from the color fundus photographs using the ImageJ program. The fundus photographs were rotated 90°. The course of the retinal arteries and veins were marked on a color fundus photograph and fitted to a second-degree polynomial curve (axe[x]/100+bx+c). The coefficient ''a'' was the width and steepness of the trajectories. The comparison between the RAT and RVT of VMT and healthy fellow eyes was investigated and the association between the RAT and RVT and the severity of disease were determined using the Image J program. RESULTS: Eleven subjects were male, and 18 subjects were female. The mean ± SD age was 70.6 ± 7.6 years. Eighteen of the eyes had VMT in the right and 11 of the eyes had VMT in the left eye. Eleven eyes were in group 1 and 18 eyes were in group 2. Axial length (AL) was similar between the two groups (22.63 ± 1.20 mm vs 22.45 ± 1.45 mm p = 0.83) (Table 1). The mean RAT was 0.60 ± 0.18 in eyes with VMT and 0.51 ± 0.17in healthy eyes (p = 0.063). The mean RVT was 0.74 ± 0.24 in eyes with VMT and 0.62 ± 0.25 in healthy eyes for the whole group (p = 0.02). In group 1, the mean RVT of the eyes with VMT was statistically significantly higher than the healthy eyes (p = 0.014). There was not any statistically significant difference for the other parameters evaluated between eyes with VMT and healthy eyes according to the groups and the whole group. (Tables 2-4) CONCLUSION: Unlike other vitreoretinal interface diseases such as epiretinal membrane and macular hole, VMT may be characterized by a narrower RVT, which is characterized by a larger "a" value.

Ocular Involvement of Brucellosis: A Pooled Analysis Study.

AIM: Brucellosis may affect the eye to varying degrees. The aim of this study was to investigate the ocular involvement of brucellosis and highlight key points. MATERIAL AND METHODS: Published literature in English language on the ocular involvement of brucellosis within last 30 years was evaluated. The PubMed international database was screened using certain keywords. RESULTS: The study included 27 publications evaluating a total of 159 cases. The most common types of ocular involvement were uveitis (52.2%) and conjunctivitis (17.6%). Most cases had concomitant systemic brucellosis (27.7%), and the most commonly used diagnostic method was a serological test (92.4%). Of all the patients, 37.1% recovered with sequelae. CONCLUSION: Brucellosis may cause a wide range of ophthalmic manifestations, and an overlooked or late diagnosis may also lead to the development of sequelae or loss of vision. A routine ophthalmologic examination should be performed in all patients with systemic brucellosis.

Comparison of Intraocular Tamponade in Patients with Peripheral Tear-Induced Retinal Detachment and Coexisting Macular Hole without High Myopia.

INTRODUCTION: To introduce the surgical results and examine the effect of intraocular tamponades on surgical outcomes in patients with coexisting macular hole (MH) and rhegmatogenous retinal detachment (RRD) without high myopia. METHODS: This retrospective, cross-sectional, two-center study was carried out with 29 eyes of 29 patients. The patients were divided into two groups according to the intraocular tamponade used in surgery: silicone oil (Group 1) and C3F8 gas (Group 2). In all patients, the internal limiting membrane was peeled during surgery. Exclusion criteria were determined as RRD with MH due to high myopia (≥ 6 D) without peripheral retinal tears and traumatic MH. RESULTS: In Group 1, the median preoperative best-corrected visual acuity (BCVA) was 3.0 (M ± SD: 2.85 ± 0.27) logMAR, while the median postoperative BCVA was 1.0 (M ± SD: 1.39 ± 0.83) logMAR (p < 0.001). In Group 2, the median preoperative BCVA was 3.0 (M ± SD: 2.37 ± 0.93) logMAR, while the median postoperative BCVA was 0.76 (M ± SD: 1.06 ± 0.86) logMAR (p = 0.008). The retinal attachment success rate was 15/17 (89.3%) in Group 1, and 11/12 (91.7%) in Group 2 (p = 0.64). The MH closure rate was 12/17 (71.6%) in Group 1, and 10/12 (78.1%) in Group 2 (p = 0.52). No difference was determined between the groups in terms of preoperative and postoperative BCVA, preoperative and postoperative intraocular pressure, and BCVA improvement. CONCLUSIONS: The study results showed no significant difference between using silicone oil or C3F8 gas as an intraocular tamponade after internal limiting membrane peeling in patients with RRD due to peripheral tear with coexisting MH.

The Importance of Anatomic Configuration and Cystic Changes in Macular Hole: Predicting Surgical Success with a Different Approach.

PURPOSE: This study aimed to define a novel metric for the area of the macular hole (MH) and cysts located around the hole using an optical coherence tomography (OCT) device. METHODS: This study was conducted with 58 eyes of 56 patients. The patients were divided into two groups according to anatomic closure after surgery. Using the metrics of macular hole index (MHI), tractional hole index (THI), hole forming factor (HFF), macular hole area (HA), the cystoid space areas in the inner retinal layers (CA), and our novel metric, the cyst hole area index (CHAI) was calculated. The correlation of the CA, the HA, and the CHAI with other indexes were assessed. Receiver operating characteristic (ROC) curves and cut-off values were derived for indexes predicting type 1 or type 2 closures. RESULTS: The CA showed a strong positive correlation with the base MH size and the maximum MH height (r = 0.624, p < 0.001; r = 0.722, p < 0.001, respectively). The HA showed a strong positive correlation with basal MH size and minimum MH size (r = 0.934, p < 0.001; r = 0.765, p < 0.001). The HA showed a moderate positive correlation with maximum MH height (r = 0.483, p < 0.001, respectively). CHAI showed a moderate positive correlation with minimum MH size (r = 0.297, p = 0.02). CHAI and HA showed a moderate negative correlation with post-operative BCVA (r = -0.39, p = 0.003; r = -0.357, p = 0.006; respectively). ROC curve analysis showed that MHI (0.823), THI (0.750), and HFF (0.722) predicted type 1 closure and that CHAI (0.769) and HA (0.709) predicted type 2 closures. CONCLUSION: MHI and our novel index CHAI, which can be calculated without any additional software, could successfully predict type 1 and type 2 closures, respectively.

Evaluation of HSP-27, BAP1, BRAF V600E, CCR7, and PD-L1 expression in uveal melanoma on enucleated eyes and metastatic liver tumors.

BACKGROUND: The presence of metastatic disease is one of the most important factors limiting survival in patients with uveal melanoma. Studies on proteins associated with metastatic mechanisms are sparse in the literature. METHODS: Enucleation samples from 15 patients with metastatic uveal melanoma (Group 1), liver metastasectomy samples from 8 patients with metastatic uveal melanoma (Group 2), and enucleation samples from 20 patients with non-metastatic uveal melanoma as controls (Group 3) were included in the study. Antibodies against heat shock protein 27 (HSP-27), BRCA1-associated protein-1 (BAP1), C-C chemokine receptor 7 (CCR7), B-Raf proto-oncogene serine/threonine-protein kinase V600E (BRAF V600E), and programmed death-ligand 1 (PD-L1) were used to detect immunoreactivity in each sample by immunohistochemical methods. Correlations between these expressed proteins and selected histopathological and clinical features, and metastatic process were investigated. RESULTS: The frequencies of HSP-27 (median score: Group 1: 8, Group 2: 12, Group 3: 4) and BRAF V600E expressions (number of samples: Group 1: 4 (26.7%), Group 2: 1 (12.5%), Group 3: 0 (0%)), and BAP1 expression loss (number of samples : Group 1: 12 (80%), Group 2: 8 (100%), Group 3: 9 (45%)) were higher in samples from patients with metastatic uveal melanoma (Group 1 + 2) than in those from patients with non-metastatic disease (Group 3) (P = 0.001, P = 0.034, and P = 0.007, respectively). CCR7 expression (median score: Group 1: 0, Group 2: 2, Group 3: 3) was similar among these three groups (P = 0.136). No samples exhibited PD-L1 expression (P = 1.000). One-unit increases in the HSP-27 expression level and BAP1 expression loss were significantly related to 1.375- and 7.855-fold increases in the risk of metastasis, respectively (P = 0.007 and P = 0.017). CONCLUSION: HSP-27 and BAP1 are considered to be associated with metastasis, indicating these proteins as potential treatment targets in metastatic uveal melanoma.

The effects of systemic aromatase inhibitors on meibomian glands and corneal structure.

OBJECTIVES: To evaluate the ocular surface, meibomian glands and corneal structural changes using in vivo confocal microscopy (IVCM) in patients receiving aromatase inhibitor (AI) therapy due to the breast cancer. METHODS: This prospective observational study included 13 patients undergoing AI therapy. The patients were evaluated before the treatment, at 3- and 6-month timepoints of AI therapy. To examine the ocular surface and tear film, corneal sensitivity (CS) measurement with Cochet-Bonnet Aesthesiometer, tear film break-up time (TBUT), lissamine green (LG) staining, Schirmer I test with anaesthesia (ST) and the ocular-surface disease index (OSDI) questionnaire were performed consecutively. Corneal cell densities and sub-basal nerve plexus were evaluated with IVCM (ConfoScan 4, Nidek, Japan). Finally, quantitative MG drop-out assessment was made using infrared meibography. Shapiro Wilk, Friedman's and Post-hoc Dunn tests were used for the statistical analysis. RESULTS: TBUT, ST scores, basal epithelium, anterior and posterior keratocytes and endothelial cell densities, long and total sub-basal nerve densities were found to be decreased (p < 0.001, p = 0.023, p < 0.001, p = 0.01, p = 0.002, p = 0.004, p < 0.001, p < 0.001), and meiboscore, CS, OSDI scores and sub-basal nerve tortuosity values were increased (p < 0.001, p = 0.015, p = 0.001, p = 0.004) during the treatment. Endothelial pleomorphism rates were lower at the 3- and 6-month timepoints compared to before the treatment (p = 0.04). CONCLUSION: This study showed that aromatase inhibitor therapy causes deteriorations in many of the ocular-surface parameters and corneal structural changes in relation with the duration of treatment. These patients should be observed during the therapy in terms of the ocular-surface side effects.

Assessment of systemic and ocular inflammation in juvenile idiopathic arthritis via choroidal vascularity index.

We aimed to evaluate the retina and the choroid in children with juvenile idiopathic arthritis (JIA) employing optical coherence tomography (OCT). This cross-sectional study, carried out between June 2017-December 2019, included JIA patients with (JIAU; n = 28) and without (JIAN; n = 65) uveitis and age-matched healthy controls (HC) (n = 102). Laboratory and demographic information of the children were obtained from hospital records. Activity of the disease was evaluated by the Juvenile Arthritis Disease Activity Score-71 (JADAS-71). Choroidal scans were obtained with spectral domain-OCT in enhanced-depth imaging (EDI)-OCT mode to assess choroidal thickness (ChT) at five locations (under the fovea, at 750 and 1500 µm nasal and temporal sections), luminal area (LA), stromal area (SA), total subfoveal choroidal area (TCA) and CVI (choroidal vascularity index). Central foveal thickness (CFT) and 1-mm diameter foveal thickness (FT) were calculated automatically through macular volume scan analysis. The choroid was significantly thicker in JIAU and JIAN patients than in HC at the subfoveal and at the 750N, 750T, 1500T points (p < 0.001, p = 0.009, p < 0.001, and p < 0.001, respectively). The CVI was lower in JIAU patients than in JIAN patients and HC (p = 0.02). Conversely, CFT was greater in JIAU patients as compared to the JIAN patients and HC (p = 0.02). Changes in chorioretinal OCT parameters in the absence of uveitis in JIA patients may reflect subclinical choroidal inflammation in these patients. Ophthalmologic examination, including choroidal imaging in a larger cohort, may clarify this aspect.

The Evaluation of Cases with Ocular Complications due to Bacillus Calmette-Guerin (BCG) Treatment using the Pool Analysis Method.

OBJECTIVE: The aim of this study was to investigate cases with ocular complications associated with intravesical BCG therapy in terms of clinical features, demographic features and type of ocular involvement. METHODS: PubMed database was scanned for relevant publications using the keywords. Thirty-seven publications and 147 reported cases were identified related to the development of ocular complications due to intravesical BCG treatment. RESULTS: As a result of the analysis performed according to eye involvement, there were 17 cases of conjunctivitis, 7 uveitis, and 5 endophthalmitis. Only 27 (18.3%) cases were of primary ocular involvement and Reiter's syndrome was present in 120 (81.6%) of all cases. CONCLUSIONS: Most of the side-effects of BCG therapy are minor and of short duration. Although rare, it has been reported that potentially serious ocular complications can develop after treatment. Physicians must keep these facts in mind and be alert to the development of ocular symptoms following BCG therapy.

Choroidal vascularity index as a biomarker of systemic inflammation in childhood Polyarteritis Nodosa and adenosine deaminase-2 deficiency.

BACKGROUND/PURPOSE: To assess EDI-OCT (enhanced depth imaging optical coherence tomography) of choroid for inflammatory signs in children with polyarteritis nodosa (PAN) and adenosine deaminase-2 deficiency (DADA-2). METHODS: In this cross-sectional study conducted between June 2017 and September 2018, we evaluated children diagnosed with PAN (n = 11) and DADA-2 (n = 4) and an age- and sex-matched control group (n = 15). Demographic and laboratory data were retrospectively analyzed from patient charts. Disease activity was assessed using the pediatric vasculitis activity score (PVAS). Choroidal images were obtained with spectral domain-OCT to measure choroidal thickness (ChT) at 5 points (750 and 1500 µm from the foveal center in the temporal and nasal quadrants and beneath the fovea), and to calculate the total subfoveal choroidal area (TCA), luminal area (LA), stromal area (SA), and the choroidal vascularity index (CVI). RESULTS: The median (min-max) age was 8 (4-16) years in PAN patients, 6 (5-16) years in DADA-2 patients and 8 (8-10) years in control group at the OCT visit (p = 0.214). The ChT at 3 points and the TCA, LA, and SA were higher in children with both PAN and DADA-2 patients compared to those of the control group (p < 0.0001, p = 0.049, p = 0.007, p = 0.007, p = 0.006, p = 0.033, respectively). The CVI was similar in both groups. No association was observed between the OCT findings, PVAS, and the erythrocyte sedimentation rate, and serum leukocyte and C-reactive protein levels. CONCLUSION: Similar CVI scores were obtained from PAN and DADA2 patients under treatment and from healthy controls. Increased subfoveal ChT without any other signs of ocular involvement may suggest choroidal thickening as a sign of mild subclinical inflammation.

Ocular Surface, Meibomian Gland Alterations, and In Vivo Confocal Microscopy Characteristics of Corneas in Chronic Cigarette Smokers.

PURPOSE: To evaluate the ocular surface, meibomian gland alterations, and in vivo confocal microscopy (IVCM) parameters through correlation with nicotine dependency level (NDL) and duration of smoking (DS) in chronic smokers. METHODS: This cross-sectional study included 50 eyes of 50 chronic smokers, and 50 eyes of 50 age- and gender-matched healthy nonsmokers. To examine the ocular surface and tear film, corneal sensitivity (CS) measurement with Cochet-Bonnet esthesiometer, tear film break-up time (TBUT), lissamine green (LG) staining, Schirmer I test with anesthesia, and Ocular Surface Disease Index (OSDI) questionnaire were performed consecutively. Basal epithelial cell, keratocyte, and endothelial cell density, the percentage of endothelial polymegethism/pleomorphism, and subbasal nerve plexus were evaluated using IVCM. Meibomian gland density was evaluated with a meibography unit. The Fagerström test was used to measure NDL, and DS was recorded. RESULTS: In the chronic smokers group, the basal epithelial cell density, anterior and posterior keratocytes, endothelial cell density, and long and total subbasal nerve numbers were lower, and LG staining, meiboscore, and OSDI scores were higher, compared with the control group, whereas other parameters were similar. The percentage of polymegethism was higher and the percentage of pleomorphism was lower in the chronic smokers group. In the correlation analysis, no significant relationship was found between the DS, NDL and ocular surface, and IVCM findings. CONCLUSION: Decreased corneal basal epithelium, anterior and posterior keratocytes, endothelial cell density, meibomian gland density, and subbasal nerve numbers were found in chronic smokers. The results of the study show that smoking has an adverse effect on ocular surface parameters.

Primary Diffuse Large B-Cell Lymphoma of the Ciliary Body.

Purpose: To report an unusual case of an eye with primary ciliary body lymphoma which came to enucleation allowing detailed histopathological examination. Methods: A 50-year-old man presented with a painful loss of vision in the left eye. The clinical, imaging, and immunohistopathological features of this case were reviewed. Results: The vision in the left eye was light perception. There were keratic precipitates, an irregular and thickened iris with neovascularization. Imaging studies disclosed a ciliary body mass extending into the anterior chamber. The eye was enucleated and immunohistopathological examination showed positive staining with CD20, BCL-2, MUM1, and CD10. Staining with BCL-6 was weak and S100 and HMB45 expressions were negative. Occasional CD3+ reactive T cells were present. The Ki-67 index was 80-90%. All these results suggested diffuse large B-cell lymphoma. Conclusions: Diffuse large B-cell lymphoma may primarily arise from the ciliary body and can develop without systemic or central nervous system disease.

Ciliary Body Mesectodermal Leiomyoma Diagnosed by Fine Needle Aspiration Biopsy.

AIMS: To describe the clinical, imaging, cytopathological, and immunohistochemical features of mesectodermal leiomyoma of the ciliary body diagnosed by fine needle aspiration biopsy in a patient who denied any major intervention without prior pathological verification. METHODS: The clinical, imaging, and cytopathological records of the patient were retrospectively reviewed. A fine needle aspiration biopsy with a 25-G needle was performed after tailoring a scleral flap. RESULTS: Examination of the cell blocks prepared from the aspirate demonstrated cells with granular cytoplasms and large nuclei. Immunohistochemical studies showed positive smooth muscle actin, desmin, h-caldesmon, CD56, and neuron-specific enolase stainings, suggesting both neurogenic and myogenic differentiation. Reactions for HMB-45, S-100, panCK, epithelial membrane antigen, glial fibrillary acidic protein, and CD68 were negative. Because the tumor continued to enlarge, fractionated stereotactic radiotherapy at the dose of 3,000 cGy was delivered, which reduced the size of the mass by 40% in 5 years. CONCLUSIONS: This case demonstrated that the diagnosis of mesectodermal leiomyoma of the ciliary body can be established with fine needle aspiration biopsy and that stereotactic radiotherapy can be successfully used to induce tumor regression.

Why and when to prefer botulinum toxin injection in childhood strabismus?

Erkan-Turan K, Taylan-Sekeroglu H, Agin A, Sanaç AS. Why and when to prefer botulinum toxin injection in childhood strabismus? Turk J Pediatr 2017; 59: 684-687. The aim of this study was to investigate the indications and outcomes of botulinum toxin injection in children with strabismus. The medical records of children who underwent botulinum toxin injection were reviewed. Eighteen patients (13 boys, 5 girls) with a mean age of 9.08±5.93 (6 months to 17 years) years were enrolled in the study. The main indication and diagnosis, initial and final deviation at primary position and the presence of abnormal head position were all evaluated. The most common diagnosis was sixth nerve palsy (7 patients) followed by Duane`s syndrome (4 patients), acquired esotropia (2 patients), acquired exotropia (2 patients), consecutive exotropia (2 patients) and sensory strabismus (1 patient). The leading indications for botulinum toxin injections were the presence of abnormal head position, diplopia and ocular misalignment at primary position. All patients received monocular injection. Fourteen patients had one, 4 patients had more than one injection. The mean follow-up period was 2.78±0.94 months for the first post-injection visit and 21.64±15.23 months for the last visit. Five patients underwent strabismus surgery due to inadequate response to injection. No complication related to injection was observed. Botulinum toxin injection may be preferred in pediatric age group particularly in case of extraocular muscle palsy, diplopia and concomitant deviation either to provide ocular alignment prior to surgery or to prevent the detrimental effect of diplopia on binocularity. The intervention seems to be safe and repeatable in children even though surgery is still inevitable in particular cases.