Exacerbation of choroidal and retinal pigment epithelial atrophy after anti-vascular endothelial growth factor treatment in neovascular age-related macular degeneration.

PURPOSE: To study the progression of retinal pigment epithelium (RPE) and choroidal atrophy in patients with neovascular age-related macular degeneration (AMD) and to assess for a possible association with the number and type of anti-vascular endothelial growth factor treatments. METHODS: Patients with neovascular AMD and a minimum of 1-year follow-up were reviewed. Fellow eyes with nonneovascular AMD were used as control eyes. Retinal pigment epithelial atrophy area and choroidal thickness were determined using spectral-domain optical coherence tomography. Multivariable regression models were used for statistical analyses. RESULTS: A total of 415 eyes were included in the study, with a mean follow-up of 2.2 years. Eyes with neovascular AMD had greater progression of RPE atrophy and choroidal atrophy compared with those with nonneovascular AMD (P < 0.001). Progression of RPE atrophy and choroidal atrophy was independently associated with the total number of injections of bevacizumab and ranibizumab (all P values ≤ 0.001). In the subgroup of 84 eyes with neovascular AMD and without RPE atrophy at baseline, only bevacizumab was associated with the progression of RPE atrophy (P = 0.003). This study likely lacked statistical power to detect an association with ranibizumab in this subgroup. CONCLUSION: Retinal pigment epithelial atrophy and choroidal atrophy in neovascular AMD seem to be exacerbated by anti-vascular endothelial growth factor treatment. Possible differences between bevacizumab and ranibizumab require further investigation.

Optical coherence tomography-based correlation between choroidal thickness and drusen load in dry age-related macular degeneration.

PURPOSE: Spectral domain optical coherence tomography can be used to measure both choroidal thickness and drusen load. The authors conducted an exploratory study using spectral domain optical coherence tomography to determine if a correlation between choroidal thickness and drusen load exists in patients with dry age-related macular degeneration. METHODS: Forty-four patients with dry age-related macular degeneration were recruited. The drusen area and volume were determined using the automated software algorithm of the spectral domain optical coherence tomography device, and choroidal thickness was measured using enhanced depth imaging. Correlations were determined using multivariable and univariable analyses. RESULTS: The authors found an inverse correlation between choroidal thickness and drusen load (r = -0.35, P = 0.04). Drusen load was also correlated with visual acuity (r = 0.32, P = 0.04). A correlation between choroidal thickness and visual acuity was suggested (r = -0.22, P = 0.21). CONCLUSION: Spectral domain optical coherence tomography can be used to assess the correlation between drusen load and choroidal thickness, both of which show a relationship with visual acuity. The measurement of these outcomes may serve as important outcome parameters in routine clinical care and in clinical trials for patients with dry age-related macular degeneration.

Comparison of endophthalmitis rates following intravitreal injection of compounded bevacizumab, ranibizumab, and aflibercept.

OBJECTIVE: Whereas the incidence of endophthalmitis after compounded intravitreal bevacizumab is known to be low, the rates of endophthalmitis after intravitreal injection of compounded ranibizumab and aflibercept are not known. The purpose of this study was to determine the incidence of endophthalmitis after treatment with compounded intravitreal ranibizumab and aflibercept and to compare this to the incidence with compounded intravitreal bevacizumab. DESIGN: Retrospective chart review. PARTICIPANTS: All patients with post-injection endophthalmitis who were seen over a 6.5-year period at a tertiary retina referral practice. METHODS: We identified all cases of endophthalmitis by searching for patients who received intravitreal antibiotics and had antecedent intravitreal injection of bevacizumab, ranibizumab, or aflibercept. RESULTS: A total of 54,101 injections of bevacizumab, 5,614 injections of ranibizumab, and 3,468 injections of aflibercept were performed. The incidence of suspected endophthalmitis was 0.041% (95% CI: 0.026-0.062) for bevacizumab, 0.036% (95% CI: 0.0043-0.13) for ranibizumab, and 0.06% (95% CI: 0.007-0.2) for aflibercept. For culture-positive cases, the incidence was 0.017% (95% CI: 0.0076-0.032) for bevacizumab, 0.02% (95% CI: 0.0005-0.1) for ranibizumab, and 0.03% (95% CI: 0.0007-0.2) for aflibercept. There was no statistically significant difference in endophthalmitis rate between the 3 different compounded drugs with respect to both overall suspected endophthalmitis rate and culture-positive endophthalmitis rate (p = 0.87). CONCLUSION: Compounding of ranibizumab and aflibercept for intravitreal use appears to be safe because the endophthalmitis rate does not appear to be different from that of intravitreal bevacizumab.

Characterization of lymphoproliferative lesions of the conjunctiva: immunohistochemical and molecular genetic studies.

BACKGROUND: Conjunctival lymphoproliferative lesions have not been selected for independent analysis with newer immunohistochemical and molecular genetic techniques to highlight their unique profile. METHODS: Retrospective case series examined biopsies from 16 consecutive patients with conjunctival lymphoproliferative lesions. The histopathologic, immunohistochemical, and molecular genetic features were characterized, as well as the frequency of tumour type, prognostic implications, clinical features, and treatments offered. RESULTS: The diagnosis was lymphoma in 12 cases, atypical lymphoid hyperplasia (ALH) in 1 case, and reactive lymphoid hyperplasia (RLH) in 3 cases. The primary lymphomas consisted of 4 mucosa-associated lymphoid tissue lymphomas (MALTL), 1 follicular lymphoma (FL), 2 diffuse large B-cell lymphomas (DLBCLs), 1 lymphoplasmacytic lymphoma, and 1 T-cell lymphoma. Primary lymphomas were treated with radiation (n = 7), surgery (n = 1), and topical chemotherapy (n = 1). Complete remission was achieved in 8 of 9 primary lymphomas. Two cases of recurrence to the other conjunctiva were treated with radiation and both remained disease free. Secondary lymphomas included 2 DLBCL and 1 MALTL. Complete remission was seen in 2 patients after radiation plus chemotherapy, while the patient treated with chemotherapy alone was lost to follow-up. The 1 case of ALH presented bilaterally and achieved complete remission after topical chemotherapy treatments. The 3 RLH cases were surgically managed and 2 of the 3 recurred and were subsequently excised. Eleven lymphomas were of B-cell lineage by immunophenotyping. Molecular genetic studies of immunoglobulin heavy chain (IgH) gene rearrangement by polymerase chain reaction (PCR) showed clonal bands in 6 of 12 lymphomas, 1 of 3 RLH (polyclonal by immunophenotyping) and 1 ALH. BCL2-IgH [t(14;18)] rearrangement was seen in 8 of 12 cases (1 FL, 3 DLBCLs, 4 MALTLs) by real-time quantitative PCR. INTERPRETATION: Conjunctival lymphomas are predominantly B-cell type with a high prevalence of MALTL. An unexpected finding was the BCL2-IgH rearrangement seen in 4 of 5 MALTL cases in our series. The significance of this remains unclear.

Alterations in intraocular cytokine levels following intravitreal ranibizumab.

OBJECTIVE: Our previous work has shown that, after intravitreal bevacizumab (IVB) administration, decreases in the levels of vascular endothelial growth factor (VEGF)-A and placental growth factor (PlGF), along with increases in the levels of interleukin (IL)-8 and transforming growth factor (TGF)-ß2, can be observed. It is not yet known if similar changes occur after intravitreal ranibizumab (IVR). The purpose of this study was to examine intraocular cytokine changes after IVR. DESIGN: Prospective clinical study. PARTICIPANTS: Subjects with proliferative diabetic retinopathy requiring pars plana vitrectomy (PPV) were recruited. METHODS: Participants received IVR as pre-treatment before PPV. Aqueous humour levels of IL-8, VEGF-A, PlGF, and TGF-ß2 were measured at time of pre-treatment and PPV. Results were analyzed using univariate statistical models. RESULTS: A total of 14 participants were recruited. After IVR administration, we observed a decrease in the levels of VEGF-A and PlGF, and an increase in the levels of IL-8 and TGF-ß2. These results were statistically significant only for VEGF-A (p = 0.0001) and IL-8 (p = 0.0002). CONCLUSIONS: The changes in cytokine levels after IVR mirror the changes seen after IVB. Further studies are warranted in order to determine if there are any differences between IVB and IVR in this regard.

Quantitative Comparison of Retinal Capillary Images Derived By Speckle Variance Optical Coherence Tomography With Histology.

PURPOSE: The purpose of this study was to correlate human retinal capillary network information derived from a prototype speckle variance optical coherence tomography (svOCT) device with histology to determine the utility of this instrument for quantitative angiography. METHODS: A retina location 3 mm superior to the optic disk was imaged with svOCT in 14 healthy human eyes. Qualitative and quantitative features of capillary networks, including capillary diameter and density, were compared with perfusion-labeled histological specimens from the same eccentricity. Twelve human donor eyes with no history of eye disease were used for histological comparisons. RESULTS: svOCT was able to clearly distinguish the morphological features of the nerve fiber layer capillary network, the retinal ganglion cell (RGC) layer capillary network, the capillary network at the border of the inner plexiform layer and superficial boundary of the inner nuclear layer, and the capillary network at the boundary of the deep inner nuclear layer and outer plexiform layer. The morphological features of these networks were highly comparable to those in previous histological studies. There were no statistical differences in mean capillary diameter between svOCT images and histology for all networks other than the RGC capillary network. Capillary density measurements were significantly greater in svOCT images, except in the RGC capillary network. CONCLUSIONS: svOCT has the capacity to provide histology-like anatomical information about human retinal capillary networks in vivo. It may have great potential as a research and diagnostic tool in the management of retinal vascular diseases. Further work is required to clarify the cause of some quantitative differences between svOCT and histology.

A randomized study comparing the efficacy of bevacizumab and ranibizumab as pre-treatment for pars plana vitrectomy in proliferative diabetic retinopathy.

BACKGROUND AND OBJECTIVE: To compare intravitreal bevacizumab versus ranibizumab as adjuvant treatment prior to pars plana vitrectomy (PPV) in proliferative diabetic retinopathy (PDR) with respect to parameters of surgical complexity. PATIENTS AND METHODS: Prospective, randomized, double-masked pilot study of patients requiring PPV for nonclearing vitreous hemorrhage or tractional retinal detachment (TRD) secondary to PDR. Patients were randomized to receive either intravitreal bevacizumab or ranibizumab at standard doses 1 week preoperatively. Measured parameters included total surgical time, presence of TRD, intraoperative bleeding, iatrogenic retinal breaks, and use of endolaser and endodiathermy or silicone oil. RESULTS: A total of 29 patients were recruited. For surgical parameters, there were no statistically significant differences between the groups in the univariate analyses. Multivariable analysis showed no statistically significant difference for total surgical time. CONCLUSION: This pilot study suggests that intravitreal bevacizumab and ranibizumab are equivalent as surgical adjuvants when used as pre-treatment in patients with PDR undergoing PPV.

Optical coherence tomography-based measurement of drusen load predicts development of advanced age-related macular degeneration.

PURPOSE: To determine whether baseline drusen load, as measured using spectral-domain optical coherence tomography (SD OCT), is a useful predictor of development of advanced age-related macular degeneration (AMD). DESIGN: Retrospective cohort study. METHODS: setting: Academic clinical practice. study population: All patients with non-neovascular AMD and no retinal pigment epithelial (RPE) atrophy at baseline who were seen between 2007 and 2012 in a single academic retina practice. A minimum of 1 year of follow-up was required. observation: Drusen load (area and volume) was assessed using automated SD OCT software algorithms. main outcome measure: RPE atrophy area, assessed using an automated SD OCT software algorithm, and the development of neovascular AMD. RESULTS: Eighty-three patients met the inclusion criteria with a mean age of 80 years and a mean follow-up time of 2.8 years. Repeated-measures analysis of variance showed an association between drusen area (P = .005) and drusen volume (P = .001) and the development of RPE atrophy. We also found an association between drusen area (P = .001) and drusen volume (P = .001) and the development of neovascular AMD. CONCLUSIONS: Drusen load, as measured using SD OCT, is associated with the development of RPE atrophy and neovascular AMD. SD OCT assessments of drusen load are simple and practical measurements that may be useful in stratifying the risk of developing advanced AMD. These measurements have potential applications in both routine clinical care and clinical trials.

Uveitis risk following oral fluoroquinolone therapy: a nested case-control Study.

OBJECTIVE: To determine the risk of uveitis associated with the use of oral fluoroquinolones. METHODS: Nested case-control study of all patients who visited an ophthalmologist in British Columbia, Canada, between 2000 and 2007, as captured in the British Columbia Health Linked Database. RESULTS: A total 3383 incident cases of uveitis and 33,830 corresponding controls were identified. Among patients who had used oral fluoroquinolones within the past 30 days, the adjusted relative risk of uveitis was 3.53 (95% CI, 2.84-4.39). However, the relative risk of uveitis among patients taking oral macrolides and beta-lactams was also significantly elevated. CONCLUSIONS: Our data do not provide convincing evidence of an association between fluoroquinolones and uveitis, as this study found an association between several classes of antibiotics and uveitis. It is possible that the systemic processes for which these antibiotics are being prescribed are in fact the inciting factors for the uveitis.

Comparative analysis of repeatability of manual and automated choroidal thickness measurements in nonneovascular age-related macular degeneration.

PURPOSE: We compared the reproducibility and mutual agreement of the subfoveal choroidal thickness measurements by expert raters and an automated algorithm in enhanced depth imaging optical coherence tomography (EDI-OCT) images of eyes with nonneovascular age-related macular degeneration (AMD). METHODS: We recruited 44 patients with nonneovascular AMD and EDI-OCT images were acquired. Subfoveal choroidal thickness was measured manually by two expert raters and automatically by a graph-cut-based algorithm. Drusen area was measured using the automated software (version 6) of Cirrus SD-OCT. The manual and automated choroidal thickness measurements were compared in reproducibility, mutual agreement, and correlation with drusen area. RESULTS: The mean subfoveal choroidal thickness was 246 ± 63 µm for the first rater, 214 ± 68 for the second rater, and 209 ± 53 for the automated algorithm. Intraclass correlation coefficients (ICC) and 95% confidence intervals (CI) were 0.96 (CI 0.94-0.98) between the raters, 0.85 (CI 0.77-0.90) between the first rater and the automated algorithm, and 0.84 (CI 0.75-0.89) between the second rater and the automated algorithm. Repeat scan measurement ICCs were 0.91 (CI 0.86-0.94) for the first rater, 0.96 (CI 0.94-0.97) for the second rater, and 0.87 (CI 0.80-0.92) for the automated algorithm. Manual and automated measurements were correlated with drusen area. CONCLUSIONS: The automated algorithm generally yielded smaller choroidal thickness than the raters with a moderate level of agreement. However, its repeat scan measurement repeatability was comparable to that of the manual measurements. The mean difference between the raters indicated possible biases in different raters and rating sessions. The correlation of the automated measurements with the drusen area was comparable to that of the manual measurements. Automated subfoveal choroidal thickness measurement has potential use in clinical practice and clinical trials, with possibility for reduced time and labor cost.

Automatic detection of subretinal fluid and sub-retinal pigment epithelium fluid in optical coherence tomography images.

Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries. Subretinal fluid (SRF) and sub-retinal pigment epithelium (sub-RPE) fluid are signs of AMD and can be detected in optical coherence tomography images. However, manual detection and segmentation of SRFs and sub-RPE fluids are laborious and time consuming. In this paper, a novel pipeline is proposed for automatic detection of SRFs and sub-RPE fluids. First, top and bottom layers of retina are segmented using a graph cut method. Then, a Split Bregman-based segmentation method is used to segment dark regions between layers. These segmented regions are considered as potential fluid candidates, on which a set of features are generated. After that, a random forest classifier is trained to distinguish between the true fluid regions from the falsely detected fluid regions. This method shows reasonable performance in a leave-one-out evaluation using a dataset from 21 patients.

Relationship between systemic cytokines and complement factor H Y402H polymorphism in patients with dry age-related macular degeneration.

PURPOSE: To investigate the relationship between systemic cytokines, the complement factor H (CFH) Y402H polymorphism, drusen load, and subfoveal choroidal thickness in patients with dry age-related macular degeneration (AMD). DESIGN: Cross-sectional study. METHODS: Forty-four dry AMD patients under care of the Retina Service at the University of British Columbia were enrolled. Drusen load was measured with an automated software algorithm in spectral-domain optical coherence tomography; subfoveal choroidal thickness was measured manually using enhanced depth imaging. Bio-Plex suspension assays (Bio-Rad Laboratories) were used to analyze cytokines in plasma and CFH Y402H was genotyped. Statistical analyses included analysis of covariance and Pearson correlation, corrected for multiple comparisons. RESULTS: The levels of 3 of 4 studied cytokines were significantly different among patients with CC, CT, or TT variants of the CFH Y402H polymorphism (P < .01). Patients with the at-risk CC variant had higher systemic levels of interleukin-6, interleukin-18, and tumor necrosis factor α than those with the CT variants, the TT variant, or both (P < .01). Interleukin-1ß did not reach significance (P = .02), but did demonstrate a consistent trend. No correlation was found between plasma cytokines and drusen load or choroidal thickness (all P > .15). CONCLUSIONS: The elevated systemic levels of selected proinflammatory cytokines, including those representing products of inflammasome activation, were associated with the CC at-risk variant of the Y402H polymorphism and suggest that genetic factors regulate the inflammatory status in dry AMD patients. Our data support the central role of inflammation in the pathogenesis of AMD and provide further evidence of a systemic involvement in AMD etiology.

Very minimal fluence photodynamic therapy for chronic central serous chorioretinopathy.

OBJECTIVE: To describe the safety and efficacy of very minimal fluence photodynamic therapy (PDT) for chronic central serous chorioretinopathy (CSC). DESIGN: Retrospective case series. PARTICIPANTS: Five patients with chronic CSC. Two had previously failed alternative therapies, and one was taking concomitant corticosteroids. METHODS: Patients were treated with very minimal fluence PDT (12 J/cm(2), 150 mW/cm(2), for 80 seconds). Median follow-up time after PDT was 100 days (range, 51 to 154). RESULTS: All patients experienced an improvement in visual acuity and symptoms, as well as complete resolution of subretinal fluid. CONCLUSIONS: Very minimal fluence PDT appears to be a safe and effective treatment for chronic CSC. Based on these preliminary findings, a randomized controlled trial is warranted.

High-definition optical coherence tomography features of primary vitreoretinal lymphoma.

Primary vitreoretinal lymphoma is a high-grade intraocular malignancy that presents as a vitritis with creamy subretinal lesions. In cases where the vitritis is dense, the characteristic subretinal lesions can be difficult to see on clinical examination. Novel high-definition imaging techniques that allow for deeper penetration through opaque media could have diagnostic utility in such cases. The authors present a case of a patient who presented with a dense vitritis that precluded visualization of fundus details. Spectral-domain optical coherence tomography using high-definition raster imaging demonstrated subretinal deposits along with outer retinal atrophy. These findings were suggestive of primary vitreoretinal lymphoma and prompted diagnostic vitrectomy. Pathological examination of the vitreous specimen confirmed the diagnosis of primary vitreoretinal lymphoma.

Macular hole repair with limited nonsupine positioning.

PURPOSE: To assess the surgical success rates of modern macular hole repair with elimination of face down positioning. METHODS: A review of data for 72 eyes (from 102 consecutive cases) with idiopathic macular holes treated surgically between 1998 and 2004 was performed. Exclusion criteria consisted of macular hole for >1 year or of unknown duration and macular holes from secondary causes. All patients were evaluated and surgically managed by one surgeon (R.T.). RESULTS: Average preoperative best spectacle corrected visual acuity (BSCVA) was 20/170 (6/51). Six patients had a grade II hole, 60 patients had a grade III hole, and 6 patients, had a grade IV hole. Anatomical success was achieved in 92% of cases with 1 operation, and the average postoperative BSCVA was 20/46 (6/14). Six patients required additional surgical management to achieve anatomical success with an average postoperative BSCVA of 20/55 (6/16.5). The postoperative BSCVA improved an average of 5.7 lines from baseline. CONCLUSION: Favorable anatomical and BSCVA outcomes were achieved with the elimination of face down positioning in the postoperative period. Additional benefits are an increase in patient acceptance and compliance and the number of patients eligible for the procedure.

Periocular petrolatum.

PURPOSE: This report describes the clinical and histopathologic features and discusses the diagnostic difficulties and management of periocular deposition of petrolatum-based materials. METHODS: Excision of orbital and eyelid tissue, tissue processing, and histopathologic examination was performed in patients with deposition of petroleum-based products. Transmission electron microscopy was performed in 3 cases. RESULTS: Between 1983 and 2003, 11 patients were diagnosed with periocular petrolatum deposition, based on clinical history and the characteristic histopathologic features of polymorphic dropout spaces, and varied from a noninflammatory lesion (paraffinoma) to those with an associated granulomatous inflammatory reaction. CONCLUSIONS: The diagnosis of petrolatum deposition can be challenging due to the range of symptoms and variable delay in presentation. Petrolatum products should be avoided during surgery and used judiciously in the postoperative period. To avoid confusion with nonspecific cases of lipogranulomatous inflammation, the terms "ointment granuloma" or "orbital paraffinoma" should be used to refer to patients presenting with orbital/eyelid lesions caused by ointment use.