Publications by authors named "Thomas M Aaberg"

41 Publications

Gene Expression Profiling in Uveal Melanoma: Five-Year Prospective Outcomes and Meta-Analysis.

Ocul Oncol Pathol 2020 Oct 6;6(5):360-367. Epub 2020 Jul 6.

Castle Biosciences, Inc., Friendswood, Texas, USA.

Introduction: The prognostic 15-gene expression profile (15-GEP) test for uveal melanoma (UM) predicts metastatic risk based on primary tumor biology. Here we report outcomes from a prospective registry of 15-GEP-tested patients, and a meta-analysis with published cohorts.

Objectives: Management and 5-year clinical outcomes following 15-GEP testing were evaluated.

Methods: Eighty-nine patients with 15-GEP results were prospectively enrolled at four centers. Physician-recommended management plans were collected, and clinical outcomes tracked every 6 months.

Results: Eighty percent of Class 1 (low-risk) patients underwent low-intensity management; all Class 2 (high-risk) patients underwent high-intensity management ( < 0.0001). Median follow-up for event-free patients was 4.9 years. Five Class 1 (10%) and 23 Class 2 (58%) tumors metastasized ( < 0.0001). Five-year Class 1 and 2 metastasis-free survival rates were 90% (81-100%) and 41% (27-62%; < 0.0001), and melanoma-specific survival rates were 94% (87-100%) and 63% (49-82%; = 0.0007). Class 2 was the only independent predictor of metastasis and was associated with increased risk for metastasis and mortality by meta-analysis.

Conclusions: UM patient management is guided by 15-GEP testing. Class 2 patients were managed more intensely, in accordance with an observed metastatic rate of >50%; Class 1 patients were safely spared intensive surveillance, resulting in appropriate utilization of healthcare resources.
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October 2020

Prepapillary vascular loop-a new classification.

Eye (Lond) 2021 02 14;35(2):425-432. Epub 2020 Apr 14.

Sydney Eye Hospital, University of Sydney, Sydney, NSW, Australia.

Background/objectives: To analyze the ophthalmic characteristics of congenital prepapillary vascular loop (PVL) and to propose a new morphologic classification dividing the loops into six types.

Subjects/methods: Collaborative multinational multicentre retrospective study of PVL cases.

Results: There was a total of 49 cases (61 eyes), 37 unilateral (75.5%) and 12 bilateral (24.5%), 32 arterial type (65.3%) and 18 venous type (36.7%) (one patient had either kind in each eye). The mean number of loops per eye was 2.7 (range, 1-7). The loops were asymptomatic in 42 cases (85.7%). Other findings included: the presence of cilioretinal artery (14 cases), retinal vascular tortuosity (26 cases), amaurosis fugax (1 case), branch retinal artery occlusion (1 case) and vitreous haemorrhage (3 cases). Six morphologic loop types could be discerned based on elevation (flat vs. elevated), shape (figure of 8 or corkscrew with hyaline sheath), number (multiple or single), location (central or peripheral), lumen size (arterial vs. arteriolar) and presence of vascular tortuosity or vitreous traction.

Conclusions: PVL are usually asymptomatic and can be divided into six morphologic types with different pathogenesis during early embryogenesis.
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February 2021

Comparative outcomes and toxicities for ruthenium-106 versus palladium-103 in the treatment of choroidal melanoma.

Melanoma Res 2018 04;28(2):120-125

Department of Radiation Oncology.

For the treatment of choroidal melanoma, palladium-103 (Pd) and ruthenium-106 (Ru) plaque brachytherapy shows reduced toxicity compared with the historical standard iodine-125. No report has directly compared the clinical outcomes between Pd and Ru, and the reasons for the selection of one over the other remain purely theoretical. Patients with choroidal melanoma with apical tumor height up to 5 mm were included. Patients from Emory University were treated with Pd between 1993 and 2012. Patients from Cleveland Clinic were treated with Ru between 2005 and 2010. Medical records were retrospectively reviewed. We compared post-treatment visual acuity (VA), toxicity, and oncologic outcomes. Pd patients (n=124) and Ru patients (n=42) had a median follow-up of 4.2 and 5.0 years, respectively. Radiation retinopathy-free survival was similar for both radioisotopes, but Ru had lower grades of retinopathy (P=0.006). Pd was associated with worse VA preservation (≥20/40) by year 3 (odds ratio: 3.8; 95% confidence interval: 1.01-14.31, P=0.048). Pd was associated with higher distant metastases-free survival (DMFS) in multivariate analysis (hazard ratio: 0.10; 95% confidence interval: 0.02-0.38; P<0.001). Ru had lower grades of radiation retinopathy and improved long-term VA preservation, but also inferior DMFS, compared with Pd. Because of the inherent limitations of a retrospective analysis, the significance of the inferior DMFS for Ru remains unclear, although the suggestion of a slight inferiority in terms of DMFS for Ru is consistent with the other limited literature. On the basis of this study, we believe that both radioisotopes remain appropriate for the treatment of small choroidal melanomas up to 5 mm in apical height.
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April 2018

Visual acuity, oncologic, and toxicity outcomes with Pd vs. I plaque treatment for choroidal melanoma.

Brachytherapy 2017 May - Jun;16(3):646-653. Epub 2017 Mar 3.

Department of Radiation Oncology and Winship Cancer Institute, Emory University, Atlanta, GA.

Purpose: To evaluate outcomes of choroidal melanoma patients treated with I or Pd plaque brachytherapy.

Methods And Materials: From 1993 to 2012, our institution treated 160 patients with Pd (56.1%) and 125 patients with I (43.9%) plaque brachytherapy. Tumor outcomes, visual acuity (VA), and toxicity were compared. Multivariate analyses (MVAs) and propensity score analysis were used to help address differences in baseline characteristics.

Results: Median followup was longer for I patients, 52.7 vs. 43.5 months (p < 0.01). At baseline, Pd patients had lower rates of VA worse than 20/200 (4.4% vs. 16%, p = 0.002), T3-T4 tumors (17.5% vs. 32.8%, p = 0.03), and transpupillary thermotherapy use (3.1% vs. 9.6%, p = 0.001). Both Pd and I provided >90% 3-year overall survival and >93% 5-year secondary enucleation-free survival. On MVA, radionuclide was not predictive for tumor outcomes. A higher percentage maintained vision better than 20/40 with Pd (63% vs. 35%, p = 0.007) at 3 years. MVA demonstrated Pd radionuclide (odds ratio [OR]: 2.12, p = 0.028) and tumor height ≤5 mm (OR: 2.78, p = 0.017) were associated with VA better than 20/40. Propensity score analysis matched 23 I with 107 Pd patients. Pd continued to predict better VA at 3 years (OR: 8.10, p = 0.014). On MVA for the development of VA worse than 20/200 or degree of vision loss, radionuclide was not significant. Lower rates of radiation retinopathy were seen with Pd than I (3 years: 47.3% vs. 63.9%, p = 0.016), with radionuclide significant in MVA.

Conclusions: Both I and Pd achieve excellent tumor control. An increased probability of long-term VA better than 20/40 and reduced risk of radiation retinopathy is associated with Pd.
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December 2017


Retin Cases Brief Rep 2017 Fall;11(4):348-351

*Dartmouth College, Hanover, New Hampshire; and †Michigan State University, Grand Rapids, Michigan.

Purpose: To describe the development of uveitis and retinal vasculitis in association with pembrolizumab treatment for metastatic uveal melanoma.

Methods: A case report and a brief review of the literature are presented. Information collected and reported include the patient's clinical course, physical examination findings, fluorescein angiogram images, retinal photographs, and her response to treatment.

Results: A 54-year-old woman was diagnosed with a large choroidal malignant melanoma and had the affected eye enucleated. Pathology confirmed a mixed cell choroidal melanoma, and gene expression profiling was Class 2. Seventeen months after enucleation, the patient was diagnosed with metastatic uveal melanoma to the liver. Disease progression was observed during ipilimumab treatment. Pembrolizumab treatment was initiated, and after four infusions, she presented to clinic complaining of floaters and blurred vision. Examination revealed a nongranulomatous panuveitis characterized by perivascular retinal pigment epithelium pigmentary changes, retinal venous sheathing, 1+ anterior chamber and vitreous cellular reaction, 2+ vitreous haze, and optic disk edema. A dexamethasone sustained-release implant was administered and the uveitis regressed. A relapse in symptoms occurred but quickly subsided with a repeat injection.

Conclusion: Pembrolizumab may induce a uveitic reaction. There is mounting evidence that patients using prembrolizumab should be educated and monitored for signs of uveitis.
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January 2018

Clinical Performance and Management Outcomes with the DecisionDx-UM Gene Expression Profile Test in a Prospective Multicenter Study.

J Oncol 2016 30;2016:5325762. Epub 2016 Jun 30.

Michigan State University Medical School and Retina Specialists of Michigan, Grand Rapids, MI 49546, USA.

Uveal melanoma management is challenging due to its metastatic propensity. DecisionDx-UM is a prospectively validated molecular test that interrogates primary tumor biology to provide objective information about metastatic potential that can be used in determining appropriate patient care. To evaluate the continued clinical validity and utility of DecisionDx-UM, beginning March 2010, 70 patients were enrolled in a prospective, multicenter, IRB-approved study to document patient management differences and clinical outcomes associated with low-risk Class 1 and high-risk Class 2 results indicated by DecisionDx-UM testing. Thirty-seven patients in the prospective study were Class 1 and 33 were Class 2. Class 1 patients had 100% 3-year metastasis-free survival compared to 63% for Class 2 (log rank test p = 0.003) with 27.3 median follow-up months in this interim analysis. Class 2 patients received significantly higher-intensity monitoring and more oncology/clinical trial referrals compared to Class 1 patients (Fisher's exact test p = 2.1 × 10(-13) and p = 0.04, resp.). The results of this study provide additional, prospective evidence in an independent cohort of patients that Class 1 and Class 2 patients are managed according to the differential metastatic risk indicated by DecisionDx-UM. The trial is registered with Clinical Application of DecisionDx-UM Gene Expression Assay Results (NCT02376920).
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July 2016

Current clinical practice: differential management of uveal melanoma in the era of molecular tumor analyses.

Clin Ophthalmol 2014 3;8:2449-60. Epub 2014 Dec 3.

Retina Consultants of Alabama and University of Alabama Birmingham, Birmingham, AL, USA.

Objective: Assess current clinical practices for uveal melanoma (UM) and the impact of molecular prognostic testing on treatment decisions.

Design: Cross-sectional survey and sequential medical records review.

Participants: Ophthalmologists who treat UM.

Methods: (A) Medical records review of all Medicare beneficiaries tested by UM gene expression profile in 2012, conducted under an institutional review board-approved protocol. (B) 109 ophthalmologists specializing in the treatment of UM were invited to participate in 24-question survey in 2012; 72 were invited to participate in a 23-question survey in 2014.

Main Outcome Measures: Responses analyzed by descriptive statistics, frequency analyses (percentages, Tukey, histograms), and Fisher's exact test. Descriptive presentation of essay answers.

Results: The review of Medicare medical records included 191 evaluable patients, 88 (46%) with documented medical treatment actions or institutional policies related to surveillance plans. Of these 88, all gene expression profiling (GEP) Class 1 UM patients were treated with low-intensity surveillance. All GEP Class 2 UM patients were treated with high-intensity surveillance (P<0.0001 versus Class 1). There were 36 (19%) with information concerning referrals after initial diagnosis. Of these 36, all 23 Class 2 patients were referred to medical oncology; however, none of the 13 Class 1 patients were referred (P<0.0001 versus Class 1). Only Class 2 patients were recommended for adjunctive treatment regimens. 2012 survey: 50 respondents with an annual median of 35 new UM patients. The majority of respondents (82%) performed molecular analysis of UM tumors after fine needle biopsy (FNAB); median: 15 FNAB per year; 2014 survey: 35 respondents with an annual median of 30 new UM patients. The majority offered molecular analyses of UM tumor samples to most patients. Patients with low metastatic risk (disomy 3 or GEP Class 1) were generally assigned to less frequent (every 6 or 12 months) and less intensive clinical visits. Patients with high metastatic risk (monosomy 3 or GEP Class 2) were assigned to more frequent surveillance with hepatic imaging and liver function testing every 3-6 months. High-risk patients were considered more suitable for adjuvant treatment protocols.

Conclusion: The majority of ophthalmologists treating UM have adopted molecular diagnostic tests for the purpose of designing risk-appropriate treatment strategies.
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January 2015

Stellate nonhereditary idiopathic foveomacular retinoschisis.

Ophthalmology 2014 Jul 22;121(7):1406-13. Epub 2014 Mar 22.

Vitreous-Retina-Macula Consultants of New York, New York.

Purpose: To describe a new classification of stellate nonhereditary idiopathic foveomacular retinoschisis (SNIFR).

Design: Retrospective case series and literature review.

Participants: A total of 17 patients from 5 institutions.

Methods: Detailed case history, multimodal imaging, and genetic testing were reviewed for patients with macular schisis without a known predisposing condition. Patients with a stellate appearance centered on the fovea with correlating confirmed expansion of the outer plexiform layer (OPL) by optical coherence tomography (OCT) were included. Exclusion criteria included a family history of macular retinoschisis, a known genetic abnormality associated with retinoschisis, myopic traction maculopathy, epiretinal membrane, vitreoretinal traction, optic or scleral pit, or advanced glaucomatous optic nerve changes.

Main Outcome Measures: Clinical features, anatomic characteristics, and visual acuity.

Results: A total of 22 eyes from 16 female patients and 1 male patient with foveomacular schisis were reviewed from 5 institutions. Initial visual acuity was ≥ 20/50 in all eyes (mean, 20/27), but visual acuity in a single eye decreased from 20/20 to 20/200 after the development of subfoveal fluid. The refractive status was myopic in 16 eyes, plano in 3 eyes, and hyperopic in 2 eyes. Three eyes had a preexisting vitreous separation, and 19 eyes had an attached posterior hyaloid. Follow-up ranged from 6 months to >5 years.

Conclusions: In this largest known series of patients with SNIFR, all patients demonstrated splitting of the OPL in the macula with relatively preserved visual acuity (≥ 20/40) except in a single patient in whom subretinal fluid developed under the fovea.
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July 2014

Bilateral choroidal tumors consistent with metastatic malignant paraganglioma.

Retin Cases Brief Rep 2013 ;7(4):301-3

*Retina Specialists of Michigan, Grand Rapids, Michigan; †Department of Neurology and Ophthalmology, Michigan State University, East Lansing, Michigan; ‡Department of Cytopathology and Clinical Pathology & Anatomic Pathology, Cleveland Clinic, Cleveland, Ohio; and §Department of Ophthalmic Oncology, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio.

Purpose: To report a patient with bilateral choroidal metastasis from a malignant paraganglioma.

Methods: Clinicopathologic case report and literature review.

Results: A 68-year-old woman presented with bilateral amelanotic focal choroidal lesions. A thorough systemic work-up for a primary cancer revealed a paraganglioma (extraadrenal pheochromocytoma) and a pheochromocytoma of the left adrenal gland. Fine-needle aspiration biopsy of the choroidal lesion was consistent with metastatic paraganglioma.

Conclusion: Metastatic paraganglioma, although rare, has the ability to metastasize to the choroid.
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January 2015

Vitreomacular traction as a consequence of posterior hyaloidal contraction after transpupillary thermotherapy.

Am J Ophthalmol 2013 May 23;155(5):937-45. Epub 2013 Jan 23.

Associated Retinal Consultants, Royal Oak, MI 48073, USA.

Purpose: To describe the pathogenesis, clinical characteristics, management, and outcomes of patients in whom vitreomacular traction evolved pursuant to treatment of choroidal melanoma with transpupillary thermotherapy.

Design: Retrospective, uncontrolled, observational, interventional case series.

Methods: Vitreomacular traction with macular distortion, macular edema, and vision loss developed in 6 eyes of 6 patients after successful transpupillary thermotherapy for choroidal melanoma. Clinical examination, fluorescein angiography, fundus photography, and spectral-domain optical coherence tomography were performed. Symptomatic patients underwent pars plana vitrectomy (PPV). Primary outcome measures include visual acuity and resolution of macular distortion by clinical examination, spectral-domain optical coherence tomography, or both.

Results: In all 6 patients, the malignant lesions were treated successfully. The posterior hyaloid was attached in all eyes before transpupillary thermotherapy. All eyes demonstrated focal hyaloidal contraction and vitreomacular traction between the transpupillary thermotherapy scar and the macula. Mean time from transpupillary thermotherapy to PPV for treatment of vitreomacular traction was 23 ± 18 months. Mean length of follow-up was 11 months. Mean logarithm of the minimal angle of resolution visual acuity before transpupillary thermotherapy was 0.23 ± 0.38. Mean visual acuity after transpupillary thermotherapy was 0.53 ± 0.42. Mean visual acuity before membrane peel was 0.65 ± 0.34. Mean visual acuity after membrane peel was 0.44 ± 0.21. All patients undergoing PPV showed visual improvement.

Conclusions: Hyaloidal contraction can occur after transpupillary thermotherapy and is a reversible cause of vision loss. The mechanism of vision loss resulting from hyaloidal contraction is flat vitreomacular traction. PPV and membrane peeling are effective in improving macular anatomic features and visual function.
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May 2013

Collaborative Ocular Oncology Group report number 1: prospective validation of a multi-gene prognostic assay in uveal melanoma.

Ophthalmology 2012 Aug 21;119(8):1596-603. Epub 2012 Apr 21.

Washington University and Siteman Cancer Center, St. Louis, Missouri, USA.

Purpose: This study evaluates the prognostic performance of a 15 gene expression profiling (GEP) assay that assigns primary posterior uveal melanomas to prognostic subgroups: class 1 (low metastatic risk) and class 2 (high metastatic risk).

Design: Prospective, multicenter study.

Participants: A total of 459 patients with posterior uveal melanoma were enrolled from 12 independent centers.

Testing: Tumors were classified by GEP as class 1 or class 2. The first 260 samples were also analyzed for chromosome 3 status using a single nucleotide polymorphism assay. Net reclassification improvement analysis was performed to compare the prognostic accuracy of GEP with the 7th edition clinical Tumor-Node-Metastasis (TNM) classification and chromosome 3 status.

Main Outcome Measures: Patients were managed for their primary tumor and monitored for metastasis.

Results: The GEP assay successfully classified 446 of 459 cases (97.2%). The GEP was class 1 in 276 cases (61.9%) and class 2 in 170 cases (38.1%). Median follow-up was 17.4 months (mean, 18.0 months). Metastasis was detected in 3 class 1 cases (1.1%) and 44 class 2 cases (25.9%) (log-rank test, P<10(-14)). Although there was an association between GEP class 2 and monosomy 3 (Fisher exact test, P<0.0001), 54 of 260 tumors (20.8%) were discordant for GEP and chromosome 3 status, among which GEP demonstrated superior prognostic accuracy (log-rank test, P = 0.0001). By using multivariate Cox modeling, GEP class had a stronger independent association with metastasis than any other prognostic factor (P<0.0001). Chromosome 3 status did not contribute additional prognostic information that was independent of GEP (P = 0.2). At 3 years follow-up, the net reclassification improvement of GEP over TNM classification was 0.43 (P = 0.001) and 0.38 (P = 0.004) over chromosome 3 status.

Conclusions: The GEP assay had a high technical success rate and was the most accurate prognostic marker among all of the factors analyzed. The GEP provided a highly significant improvement in prognostic accuracy over clinical TNM classification and chromosome 3 status. Chromosome 3 status did not provide prognostic information that was independent of GEP.
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August 2012

Ophthalmic and systemic findings in interstitial deletions of chromosome 14q: a case report and literature review.

Ophthalmic Genet 2012 09 9;33(3):161-6. Epub 2012 Apr 9.

Michigan State University, Metro Health Hospital, WY 49519, USA.

We report a patient with clinical anophthalmia, partial eyelid fusion and a hypoplastic socket on the right. The left eye has microphthalmia involving the anterior and posterior segments, microcornea, iris coloboma, chorioretinal dysgenesis, macular dysplasia, absence of retinal vessels, and optic nerve aplasia. Systemic abnormalities include microcephaly, bilateral hearing loss, and duodenal atresia. Electrophysiologic testing showed no response from either eye. Cytogenetic testing revealed a de novo interstitial deletion of chromosome 14q22.3q23.1. The literature of similar interstitial deletions and ongoing candidate gene studies are reviewed.
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September 2012

Retinoblastoma in a 48-year-old woman.

Retin Cases Brief Rep 2011 ;5(1):22-5

From the *Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia; †Retina Specialists of Michigan, Grand Rapids, Michigan; ‡Ocular Oncology Service, Wills Eye Institute, Philadelphia, Pennsylvania; and §Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan.

Purpose: The purpose of this study was to describe an unusual presentation of retinoblastoma in an adult.

Methods: Retrospective case report.

Results: A 48-year-old woman with floaters was found to have an amelanotic intraocular mass with localized vitreous seeds in the superior fundus. Metastatic workup was negative. Cytologic examination of the vitrectomy specimen showed a malignant neoplasm with neuroendocrine differentiation, suspicious for carcinoid tumor. The patient later was found to have a lung lesion presumed to be a carcinoid tumor. She was treated with external beam radiation to the eye, but 1 year later, a new retinal tumor was discovered inferiorly requiring plaque radiotherapy. Soon thereafter, she developed massive intraocular recurrence. The eye was enucleated. Histopathology revealed small round blue cells with round hyperchromatic nuclei. Rosettes were also present within the tumor consistent with retinoblastoma.

Conclusion: Late-onset retinoblastoma can occur in adults, and the diagnosis can be challenging.
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November 2014

Residual triamcinolone acetonide sequestered in the fovea after macular hole repair.

Retina 2011 Jan;31(1):148-53

Department of Vitreoretinal Surgery and Disease, Emory University, Atlanta, GA, USA.

Purpose: To report the macular hole closure rate and visual outcomes of patients with residual triamcinolone acetonide in the fovea after macular hole repair.

Methods: We reviewed the medical records of consecutive patients who underwent macular hole surgery at our institution between 2005 and 2008. Only patients with visible triamcinolone in the fovea in the first postoperative month were included.

Results: Six patients with Stage III or IV macular holes were included. All patients underwent pars plana vitrectomy, internal limiting membrane peeling, and gas tamponade. Triamcinolone acetonide was used to visualize the vitreous in every patient, and diluted indocyanine green was used to stain the internal limiting membrane in five patients. The median preoperative best-corrected visual acuity was 20/200, which improved to a median of 20/40 at the last follow-up. Five patients eventually developed retinal pigment epithelial alterations. Anatomic hole closure was achieved in every patient. The mean follow-up was 23 months (range, 3-36 months).

Conclusion: Residual triamcinolone sequestered in the fovea after macular hole surgery did not affect hole closure or prevent improvement in visual acuity. It is unclear whether the retinal pigment epithelial alterations in our patients represent toxicity or are unrelated to the triamcinolone exposure.
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January 2011

Surgery as the primary management of proliferative vitreoretinopathy: a history reflecting my experiences and biases.

Thomas M Aaberg

Arch Ophthalmol 2010 Aug;128(8):1068-70

Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA 30322, USA.

Although attempts were made ot reattach retinas using proliferative vitreoretinopathy by various techniques before the 1970s, it was the development and subsequent refinement of closed-eye, mechanized pars plana vitrectomy that initiated the rapid rise in the surgical success rate. This article presents a personal history of the milestone accomplishments that facilitated the strong possibility of success that patients with proliferative vitreoretinopathy can now anticipate. Currently, various gasses, chemical compounds, and pharmaceutical agents serve adjunctively to advance surgical techniques with the expectation that they may be the primary curative procedure in the future. As in the past, what is unconventional today may be common tomorrow.
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August 2010

Clinical characteristics of hydroxychloroquine retinopathy.

Br J Ophthalmol 2011 Feb 7;95(2):245-50. Epub 2010 Aug 7.

Emory Eye Center, Atlanta, GA 30322, USA.

Aims: To assess the characteristics and outcomes of patients with hydroxychloroquine retinopathy and to review the current screening guidelines.

Methods: Retrospective chart review of patients diagnosed as having hydroxychloroquine retinopathy at our institution between 2004 and 2008.

Results: All seven patients were women. While every patient received 400 mg of hydroxychloroquine per day, every patient exceeded the recommended daily dosage allowance (6.5 mg/kg/day). The mean daily dose of hydroxychloroquine was 8.2 mg/kg/day (range: 6.8-13.6 mg/kg/day). The mean duration of usage was 16.3 years (range: 8.5-30 years), and the mean cumulative dose was 2377 g (range: 1241-4380 g). The mean visual acuity at presentation was 20/30, but all patients exhibited significant visual-field defects. Colour vision was impaired in six patients. Four patients exhibited granular hyperpigmentation in the central macula, and three had a bull's eye appearance. The mean follow-up time was 21 months. The visual outcomes remained stable for every patient except for one patient who experienced an improvement in visual function after drug cessation.

Conclusions: Hydroxychloroquine retinopathy, although rare, still exists despite current screening guidelines. The authors recommend that physicians dose hydroxychloroquine according to lean body weight and that they use risk stratification to guide their screening regimens.
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February 2011

Visual outcomes and incidence of recurrent vitreous hemorrhage after vitrectomy in diabetic eyes pretreated with bevacizumab (avastin).

Retina 2009 Jul-Aug;29(7):926-31

Department of Ophthalmology, Emory University, Atlanta, Georgia, USA.

Purpose: To evaluate the safety and effect of bevacizumab pretreatment on the incidence of recurrent vitreous hemorrhage and visual acuity after vitrectomy for proliferative diabetic retinopathy.

Methods: This was a consecutive, retrospective, and comparative cohort study. Patients undergoing vitrectomy from September 2006 through November 2007 at the Emory Eye Center for complications of proliferative diabetic retinopathy were identified and reviewed. A total of 33 eyes pretreated with bevacizumab and 104 untreated eyes were observed for postoperative vitreous hemorrhage and final visual acuity.

Results: Patients in the bevacizumab group were significantly younger than those in the untreated group (average age, 46.4 vs. 58.4 years) and were more likely to have 20-gauge instrumentation (58% vs. 36%). An average of 9.6 days passed between injection and surgery. Early (4-6 weeks) rebleed rates were 15% versus 13% in the bevacizumab and untreated groups, respectively, and not statistically different. Preoperative (7/200 vs. count finger at 4'), 1-month postoperative (20/200(-3) vs. 20/150), and 3-month postoperative visual acuity (20/100(-3) vs. 20/100(+2)) were not statistically different between groups. No statistical difference was found in rebleed rates regarding the gauge of vitrectomy.

Conclusion: Bevacizumab pretreatment for diabetic vitrectomy was not associated with any observed complications but did not influence rates of postoperative vitreous hemorrhage or final visual acuity in this retrospective series. The overall incidence of postoperative early vitreous hemorrhage in this series was 13% and seems lower than historically reported rates.
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October 2009

Incidence of postvitrectomy macular edema using optical coherence tomography.

Ophthalmology 2009 Aug 5;116(8):1531-7. Epub 2009 Jun 5.

Department of Ophthalmology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.

Objective: To evaluate the incidence, effect on visual recovery, and predisposing risk factors of postvitrectomy macular edema (ME).

Design: Prospective cohort study.

Participants: One-hundred nine eyes undergoing nonemergent vitrectomy surgery.

Methods: Eyes were evaluated for postoperative day 1 inflammation, 1-month retinal thickness using optical coherence tomography, and preoperative and 1-month postoperative best-corrected visual acuity (BCVA). Macular edema was defined as central subfield thickness > or =272 microm.

Main Outcome Measures: Retinal thickness, inflammation, and BCVA.

Results: Incidence of ME on optical coherence tomography was 47% (95% confidence interval [CI], 37%-56%). Mean 1-month visual acuity improved 3.3 lines (0.33 logarithm of minimum angle of resolution [logMAR] units) to 20/80(+1) (0.58+/-0.46 logMAR units) from 20/150(-2) (0.91+/-0.63 logMAR units) before surgery (P<0.001). Mean 1-month center point thickness (CPT), central subfield (CSF), and total macular volume were 265+/-107 microm, 288+/-94 microm, and 7.8+/-1.2 mm(3), respectively. Severity of postoperative inflammation predicted retinal thickness at 1 month (P<0.05). Intraoperative epinephrine use was associated with increased postoperative inflammation (P = 0.02). Eyes with greater reduction in CSF (or CPT) from baseline experienced more rapid visual recovery (r = -0.36; 95% CI, -0.61 to -0.06; P = 0.02).

Conclusions: Postvitrectomy ME is common and delays visual recovery. Degree of postoperative inflammation is an important risk factor for ME and, in this series, was increased in the setting of intraocular epinephrine. Efforts to reduce or prevent inflammation after vitrectomy should be beneficial and therefore are encouraged.
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August 2009

Topical ketorolac in vitreoretinal surgery: a prospective, randomized, placebo-controlled, double-masked trial.

Arch Ophthalmol 2008 Sep;126(9):1203-8

Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia, USA.

Objective: To evaluate the effects of topical ketorolac in patients undergoing vitreoretinal surgery.

Methods: One hundred nine patients undergoing vitrectomies were randomized to receive either topical ketorolac tromethamine, 0.4%, or placebo. Patients were instructed to begin taking the study medication 3 days preoperatively (4 times daily) and to continue taking it 4 weeks postoperatively.

Main Outcome Measures: Intraoperative pupil diameter, postoperative day 1 pain and inflammation, 1-month postoperative retinal thickness, and preoperative and 1-month postoperative best-corrected visual acuities.

Results: The difference in mean pupil diameters between patients using ketorolac and those taking placebo was 0.06 mm (P = .39). Patients taking ketorolac and those taking placebo had mean pain scores (scale, 1-10) of 0.24 (SD, 0.6) and 1.06 (SD, 2) (P = .03) and mean inflammation grades (grade, 0-4) of 0.59 (SD, 0.7) and 1.16 (SD, 0.9) (P < .001), respectively. Ketorolac reduced central subfield thickness by 8%, but this was not statistically significant. At 1 month, mean visual acuities improved to 0.40 logMAR units (mean Snellen, 20/50; SD, 0.28 logMAR units) in the ketorolac group from 0.83 logMAR units (20/150(+2); SD, 0.60 logMAR units) at baseline and to 0.67 logMAR units (20/100(+1); SD, 0.46 logMAR units) in the placebo group from 0.92 logMAR units (20/150(-2); SD, 0.62 logMAR units) at baseline (P = .001).

Conclusions: Topical ketorolac was well tolerated and safe, reduced postoperative pain and inflammation, and improved visual recovery in this prospective, double-masked trial.

Application To Clinical Practice: Topical ketorolac may benefit patients undergoing vitreoretinal surgery.

Trial Registration: Identifier: NCT00576329.
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September 2008

Clinicopathologic correlations in eyes enucleated after uveal melanoma resection with positive surgical margins.

Indian J Ophthalmol 2007 Sep-Oct;55(5):380-3

Department of Ophthalmology and Pathology, Emory University School of Medicine, Atlanta, Georgia, USA.

We identified three eyes that had undergone enucleation after transscleral resection of uveal melanoma. Two enucleated eyes with microscopically positive margins of resection exhibited no evidence of residual melanoma and these patients were alive without metastasis with at least four years' follow-up. One eye with a transected melanoma contained residual melanoma and that patient died with metastatic melanoma to the liver three years after enucleation. There appear to be at least two general types of positive surgical margins of resection of uveal melanoma: microscopically positive margins and macroscopically positive (transected) margins of resection.
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November 2007

Diagnostic and therapeutic challenges.

Retina 2007 Jun;27(5):642-7

Department of Ophthalmology, Manhattan Eye, Ear and Throat Hospital and NYU School of Medicine, New York, NY, USA.

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June 2007

Ischemic necrosis and atrophy of the optic nerve after periocular carboplatin injection for intraocular retinoblastoma.

Am J Ophthalmol 2006 Aug;142(2):310-5

Emory Eye Center, Emory University School of Medicine, Atlanta, Georgia 30322, USA.

Purpose: To report four cases of optic nerve neuropathy in three children treated with periocular carboplatin injections for unilateral or bilateral intraocular retinoblastoma.

Design: Retrospective, observational case series.


Setting: University-based Ophthalmology Practice.

Study Population: Four eyes of three children with retinoblastoma enucleated after nonsuccessful multimodality treatment including periocular carboplatin injections.

Observation Procedures: The enucleated eyes were routinely processed and evaluated by light microscopy. A retrospective chart review of all four cases was performed.

Results: Three enucleated eyes (Reese-Ellsworth groups III and VB) were obtained from two children with bilateral multifocal retinoblastoma, and one eye (Reese-Ellsworth group IIB) was harvested from a child with unilateral retinoblastoma. All affected eyes underwent three to seven periocular carboplatin injections before enucleation. Additional treatment modalities included systemic chemotherapy, transpupillary thermotherapy, transscleral cryotherapy, and external beam radiotherapy. Histopathologic evaluation of the enucleated eyes revealed focal areas of ischemic necrosis or atrophy of the optic nerve along with dystrophic calcification and mild inflammation in the surrounding fibrovascular adipose tissue.

Conclusions: Periocular injections of carboplatin may be a useful treatment approach in the management of patients with advanced intraocular retinoblastoma and may minimize systemic side-effects. However, ophthalmologists and pediatric oncologists should be aware of potential marked local complications with periocular carboplatin delivery, including ischemic optic neuropathy. Modifying the injection site/location (for example, subtenon space) or adding other delivery routes adjuncts (for example, fibrin sealant) deserves further study.
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August 2006

Laser for choroidal melanoma.

Thomas M Aaberg

Int Ophthalmol Clin 2006 ;46(1):15-26

Associated Retinal Consultants, Grand Rapids, MI 49546, USA.

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March 2006

Subconjunctival carboplatin in fibrin sealant in the treatment of transgenic murine retinoblastoma.

Ophthalmology 2005 Jun;112(6):1151-8

Ocular Oncology Unit, Department of Ophthalmology, University of California at San Francisco, San Francisco, California 94143, USA.

Purpose: To evaluate the efficacy of subconjunctival carboplatin in fibrin sealant in the treatment of transgenic murine retinoblastoma.

Design: Experimental study using LHbeta-Tag transgenic mice in a randomized controlled trial.

Participants And Controls: Thirty-three 10-week-old LHbeta-Tag transgenic mice: 22 carboplatin-treated animals and 11 control animals.

Methods: Three groups of 11 mice were treated with a single, 30 microl injection of fibrin sealant in the subconjunctival space of 1 eye; the opposite eye was left untreated as an internal control. Group 1 (low-dose group) received 37.5 mg/ml calculated concentration of carboplatin in fibrin sealant (0.66 mg measured total dose). Group 2 (high-dose group) received 75 mg/ml calculated concentration of carboplatin in fibrin sealant (1.23 mg measured total dose). Group 3 (control group) received fibrin sealant only. Mice were killed on day 22 after treatment. Eyes were serially sectioned, and retinal tumor burden was quantified by histopathologic analysis. For statistical analysis of treatment effects, eyes were divided into 6 groups: low-dose group, sealant-treated eyes; low-dose group, untreated eyes; high-dose group, sealant-treated eyes; high-dose group, untreated eyes; control group, sealant-treated eyes; and control group, untreated eyes.

Main Outcome Measures: Main outcome measure was mean tumor burden per level per eye in each experimental group.

Results: The best therapeutic results were obtained in eyes treated with low-dose carboplatin in fibrin sealant, where no histopathologic evidence of toxicity was observed, and 6 of 11 eyes had zero tumor burden. Tumor burden in the remaining 5 eyes in this group was minimal (4 eyes) or moderate (1 eye) compared with mean control values. Mean tumor burden in this group was significantly smaller than mean tumor burden in untreated eyes from the same mice (P<0.004), sealant-treated eyes in the control group (P<0.004), and untreated eyes in the control group (P<0.002). Although a similar reduction in mean tumor burden was observed in eyes treated with high-dose carboplatin in fibrin sealant, 5 of 10 eyes analyzed in this group also demonstrated histopathologic evidence of severe toxicity.

Conclusions: Subconjunctival carboplatin in fibrin sealant is effective in the treatment of transgenic murine retinoblastoma. A single injection of low-dose carboplatin in fibrin sealant was sufficient to induce complete or near-complete intraocular tumor regression in 10 of 11 eyes (91%), with no associated histologic evidence of toxicity. These results suggest that subconjunctival carboplatin in fibrin sealant provides sustained release and could have clinical use in the treatment of intraocular retinoblastoma.
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June 2005

Three cases of large retinal capillary hemangiomas treated with verteporfin and photodynamic therapy.

Arch Ophthalmol 2005 Mar;123(3):328-32

Associated Retinal Consultants, Grand Rapids, Mich, 49546, USA.

Objective: To investigate the efficacy of verteporfin and photodynamic therapy in the treatment of large retinal capillary hemangiomas.

Methods: Case reports of 3 patients with large retinal capillary hemangiomas treated with photodynamic therapy using verteporfin. Standard verteporfin dosages (6 mg/m(2) of body surface area) were given. Both standard and modified photodynamic protocols were followed. Modified protocols included shorter verteporfin infusion times and longer light exposure times.

Results: Pretreatment best-corrected Snellen visual acuity of the 3 affected eyes were 20/100, 20/50, and 2/200, respectively. All cases had associated exudative retinal detachments involving the macula. Cases 1 and 2 were classic endophytic retinal capillary hemangiomas. Case 3 was a reactive retinal capillary hemangioma. Case 1 had 2 photodynamic therapy treatments, and after 8 months, visual acuity improved to 20/40. Two years after initiating photodynamic therapy, the visual acuity was 20/30 and there was no reperfusion of the hemangioma. Case 2 had 3 photodynamic therapy treatments. The hemangioma was fibrotic, and 20 months after initiating photodynamic therapy visual acuity improved to 20/30. Case 3 had 1 treatment, 11 weeks later and visual acuity improved to 20/400. Four months after treatment, visual acuity returned to counting fingers because of tractional elevation of the macula as the capillary hemangioma fibrosed. Vitrectomy surgery was performed, and choroidal and retinal neovascularization was discovered. Three months after vitrectomy visual acuity was 20/400. In cases 1 and 2, the capillary hemangioma ultimately regressed, and the exudative detachment resolved.

Conclusions: Verteporfin and photodynamic therapy were effective in achieving closure of large retinal capillary hemangiomas. In all cases, the hemangioma underwent fibrosis with consequent macular puckering due to retinal traction. In all cases, the visual acuity improved.
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March 2005

Photodynamic therapy with verteporfin in ocular histoplasmosis: uncontrolled, open-label 2-year study.

Ophthalmology 2004 Sep;111(9):1725-33

Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami School of Medicine, Miami, FL 33136, USA.

Objective: To evaluate the safety, effect on visual function, and fluorescein angiographic appearance of subfoveal choroidal neovascularization (CNV) through 2 years after photodynamic therapy with verteporfin (Visudyne; Novartis AG, Basel, Switzerland) in patients with ocular histoplasmosis syndrome (OHS).

Design: Open-label, 3-center, uncontrolled clinical study.

Participants: Ocular histoplasmosis syndrome patients with subfoveal CNV (N = 26) with a greatest linear dimension no larger than 5400 microm with classic or occult CNV extending under the geometric center of the fovea, and best-corrected visual acuity letter score of approximately 20/40 to 20/200.

Methods: The methods were similar to those described in the 1-year results with follow-up examinations every 3 months continuing through the second year. During the second year, additional therapy was recommended if fluorescein angiography showed leakage at a scheduled visit.

Main Outcome Measurements: Visual function measurements included the changes from baseline in visual acuity and contrast sensitivity scores. Lesion size and leakage from classic and occult CNV were assessed at month 12 and month 24. Safety assessments also were made.

Results: A 24-month examination was completed in 22 of the 26 enrolled participants (85%). At the 24-month examination, median improvement from baseline in visual acuity of the 22 patients evaluated was 6 letters; median contrast sensitivity improved by 3.5 letters. At the 24-month examination, 10 patients (45%) gained 7 or more letters of visual acuity from baseline, whereas 4 patients (18%) lost 8 or more letters, including 2 patients (9%) who lost at least 15 letters. There was absence of fluorescein angiographic leakage from classic CNV in 17 of the 20 evaluable lesions (85%), and leakage from occult CNV was absent in all eyes. No serious ocular adverse events were reported, and no serious systemic event was considered to be associated with treatment.

Conclusions: Median visual acuity improved and fluorescein angiographic leakage decreased after verteporfin therapy in this small, uncontrolled clinical study of patients with subfoveal CNV resulting from OHS. Verteporfin therapy seemed to be relatively safe in these patients. The selected cases feature fluorescein angiographic examples of CNV that are important in determining when to apply verteporfin therapy.
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September 2004

Recurrent vitreous hemorrhage after sutured posterior chamber intraocular lenses.

Retina 2004 Apr;24(2):193-8

California Pacific Medical Center, San Francisco, CA, USA.

Purpose: To describe the clinical course and management of patients with late vitreous hemorrhage after scleral suturing of posterior chamber intraocular lenses (PCIOL).

Methods: The authors reviewed patient demographics, ocular findings, and clinical course of six patients with late (>3 weeks) vitreous hemorrhage after sclera-sutured PCIOL. Intraoperative endoscopy was performed on two patients to better assess the haptic sulcus interaction.

Results: Patient age ranged from 39 to 84 years (median 77 years). The interval between scleral suturing of the PCIOL and vitreous hemorrhage ranged from 3 weeks to 68 months (median 5 months). The number of hemorrhages ranged from one to four. The hemorrhage cleared spontaneously in three eyes. Three patients underwent surgery after the hemorrhages including sutured PCIOL removal with concurrent placement of an anterior chamber IOL (ACIOL) (two patients) and resuturing of a PCIOL in a different meridian (one patient). Follow-up ranged from 4 to 36 months, median 19.5 months, starting from the time of the initial postsuturing vitreous hemorrhage. Final vision ranged from 20/20 to hand motions, with four eyes having 20/40 or better vision. Endoscopy revealed a haptic embedded into the pars plicata in one eye but no evidence of neovascularization.

Conclusion: Recurrent vitreous hemorrhage may occur as a complication of scleral suturing of PCIOL. The etiology of these hemorrhages does not appear to be related to neovascular proliferation at the haptic suture site, but may be secondary to erosion of the haptic into uveal structures. Not all eyes require reoperation after these hemorrhages; however, good visual results may be achieved by replacing the sutured PCIOL with an ACIOL or by suturing the PCIOL in a different meridian.
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April 2004