Comparison of Three Different Techniques of Inverted Internal Limiting Membrane Flap in Treatment of Large Idiopathic Full-Thickness Macular Hole.

Purpose: To evaluate and compare three different techniques of inverted internal limiting membrane (ILM) flap in the treatment of large idiopathic full-thickness macular hole. Methods: In a comparative interventional case series, 72 eyes from 72 patients with large (\u3e 400 µm) full-thickness macular hole were randomly enrolled into three different groups: group A - hemicircular ILM peel with temporally hinged inverted flap; group B - circular ILM peel with temporally hinged inverted flap; and group C - circular ILM peel with superior inverted flap. Best-corrected visual acuity (BCVA), anatomical closure rate, and ellipsoid zone (EZ) or external limiting membrane (ELM) defects were evaluated preoperatively, at week 1, and months 1, 3 and 6 after surgery. Results: There were 24 eyes in group A, 23 in group B, and 25 in group C. In all three groups, larger diameter macular hole was associated with worse preoperative visual acuity (r=0.625, P\u3c0.001). Mean BCVA improved significantly in all three groups 6 months after surgery (0.91vs 0.55, p\u3c0.001). 6 months after surgery, mean BCVA improved from 0.91 logMAR to 0.52±0.06 in group A, 0.90 to 0.53±0.06 in group B, and 0.91 to 0.55±0.11 in group C. In group A vs. B vs. C, improvement of BCVA was 0.380±0.04 vs. 0.383±0.04 vs. 0.368±0.11 logMAR, with no statistically significant difference between groups (P=0.660). The rate of successful hole closure was 87.5% vs. 91.3% vs. 100%. Although the closure rate was 100% in Group C (circular ILM peel with superiorly hinged inverted flap), this difference was not statistically significant (P=0.115). Conclusion: ILM peel with an inverted flap is a highly effective procedure for the treatment of large, full-thickness macular hole. Different flap techniques have comparable results, indicating that the technique can be chosen based on surgeon preference

Conjunctival Melanoma: Features Based on the Fitzpatrick Skin Type (FST) in 540 Patients at a Single Ocular Oncology Center

Background: The Fitzpatrick skin type (FST) is a classification system for skin pigmentation that has been used to stratify risk for cutaneous melanoma; however, it has not yet been explored in the context of conjunctival melanoma. Herein, we examine FST and its association with the clinical features of conjunctival melanoma. Methods: A retrospective review was conducted on 540 medical records of patients with pathologic diagnosis of conjunctival melanoma. The patients were categorized according to the FST classification based on their external facial photographs at presentation. This includes: Type I (white skin color), Type II (fair skin color), Type III (average skin color), Type IV (light-brown skin color), Type V (brown skin color), and Type VI (black skin color). Other clinical features (namely tumor characteristics, tumor location, and tumor color) were also noted. Results: The FST included Types I (n=126, 23%), II (n=337, 62%), III (n=56, 10%), IV (n=8, 2%), V (n=12, 2%), and VI (n=1, \u3c1%). Statistical analysis (FST I vs. FST II vs. FST III, IV, V, and VI) revealed FST I and II tumors had smaller tumor thickness (2.1 vs. 2.8 vs. 3.6 mm, p=0.01) and less eyelid involvement (13% vs. 13% vs. 28%, p=0.02). Discussion: In this analysis, we found that the majority of patients with conjunctival melanoma are FST I or II; they also had smaller tumor thickness and less eyelid involvement than FST III, IV, V, and VI. Thus, patients with FST I and II should be considered a phenotype at risk for conjunctival melanoma and be observed accordingly

Photodynamic Therapy in Ocular Oncology

Over the past two decades, we have witnessed the increasing use of photodynamic therapy (PDT) in the field of ocular oncology. Based on a review of the literature and our own experience, we herein review the role of PDT for the management of intraocular tumors. The discussion includes two main topics. First, we discuss the application of PDT for benign tumors, including circumscribed choroidal hemangioma, choroidal osteoma, retinal astrocytoma, retinal capillary hemangioma (retinal hemangioblastoma), and retinal vasoproliferative tumor. Second, we assess the role of PDT for malignant tumors, including choroidal melanoma and choroidal metastasis

White paper on ophthalmic imaging for choroidal nevus identification and transformation into Melanoma

Purpose: To discuss the evolution of noninvasive diagnostic methods in the identification of choroidal nevus and determination of risk factors for malignant transformation as well as introduce the novel role that artificial intelligence (AI) can play in the diagnostic process. Methods: White paper. Results: Longstanding diagnostic methods to stratify benign choroidal nevus from choroidal melanoma and to further determine the risk for nevus transformation into melanoma have been dependent on recognition of key clinical features by ophthalmic examination. These risk factors have been derived from multiple large cohort research studies over the past several decades and have garnered widespread use throughout the world. More recent publications have applied ocular diagnostic testing (fundus photog-raphy, ultrasound examination, autofluorescence, and optical coherence tomography) to identify risk factors for the malignant transformation of choroidal nevus based on multimodal imaging features. The widespread usage of ophthalmic imaging systems to identify and follow choroidal nevus, in conjunction with the characterization of malignant transformation risk factors via diagnostic imaging, presents a novel path to apply AI. Conclusions: AI applied to existing ophthalmic imaging systems could be used for both identification of choroidal nevus and as a tool to aid in earlier detection of transformation to malignant melanoma. Translational Relevance: Advances in AI models applied to ophthalmic imaging systems have the potential to improve patient care, because earlier detection and treatment of melanoma has been proven to improve long-term clinical outcomes

CyberKnife Robotic-Assisted Stereotactic Radiosurgery for Advanced Stages of Ciliochoroidal Uveal Melanoma. Preliminary Results in Mexico

Objective: The objective of this study was to report the early results of CyberKnife® (CK®) stereotactic radiosurgery in advanced stages of ciliochoroidal (CBCh) melanoma in Mexican patients. Methods: A retrospective review of charts was performed to analyze the outcomes of patients who underwent CK® (Accuray Inc, Sunnyvale, CA, United States). Results: Four patients with CBCh melanoma were treated under this protocol. The mean age was 53.2 ± 5.3 years (range, 47-60). Median of follow-up was 9.5 ± 3.1 months (range, 5-12). Mean tumor diameter was 13.49 mm, mean thickness, 11.74 mm, and mean gross tumor volume was 1251.97 mm3. Tumors were dome- (50%) and mushroom-shaped (50%) in medium-to-large sizes. Three patients had T3b tumors, and one had a T4d tumor at the early tumor staging according to the American Joint Committee on Cancer. A mean dose of 2763 ± 181.3 cGy was prescribed to the 90% isodose line. All patients achieved local tumor control after single-session radiosurgery at the latest follow-up. One patient presented with acute toxicity (extensive serous retinal detachment associated with radiation induced tumor vasculopathy) that was promptly managed. None of the patients required secondary enucleation. Conclusions: CK® appears to be an effective therapy for medium to large-sized CBCh melanoma. A prospective comparative study with longer follow-up is needed to confirm these findings and to evaluate long-term morbidity

Editorial – Thiolated Chitosan-carboxymethyl Dextran Nanoparticles: Improving Intravitreal Drug Bioavailability for Retinoblastoma

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Orbital and external ocular manifestations of Mycobacterium tuberculosis: A review of the literature

Tuberculosis (TB) is an airborne infectious disease caused by Mycobacterium tuberculosis that most commonly affects the lungs. However, extrapulmonary manifestations of TB can affect the eye and surrounding orbital tissues. TB can affect nearly any tissue in the eye, and a high index of suspicion is required for accurate diagnosis. Systemic anti-tuberculosis treatment is required in cases of ocular TB, and steroids are sometimes necessary to prevent tissue damage secondary to inflammation. Delays in diagnosis are common and can result in morbidities such as loss of an affected eye. It is important for ophthalmologists and infectious disease specialists to work together to accurately diagnose and treat ocular TB in order to prevent vision loss. This article reports the various known presentations of orbital and external ocular TB and reviews important elements of diagnosis and treatment. Keywords: Tuberculosis, Mycobacterium, Orbit, Eye, Ocula

Intraocular manifestations of mycobacterium tuberculosis: A review of the literature

Mycobacterium tuberculosis: is most commonly associated with pulmonary infection. However, tuberculosis (TB) can also affect the eye. TB can affect nearly any tissue in the eye, and a high index of suspicion is required for accurate diagnosis, as many of the intraocular manifestations of TB can mimic other, more common diseases. Correct diagnosis is critical because systemic anti-tuberculosis treatment may be required, and vision loss or even loss of the affected eye can occur without proper treatment. Thus, it is important for ophthalmologists and infectious disease specialists to work together to accurately diagnose and treat intraocular TB. This article reports the various known presentations of intraocular TB and reviews important elements of diagnosis and treatment. Keywords: Mycobacterium, Tuberculosis, Choroidal granuloma, Retinal vasculiti

Prognostication of uveal melanoma is simple and highly predictive using The Cancer Genome Atlas (TCGA) classification: A review.

Purpose: The cancer genome atlas (TCGA) is a comprehensive project supported by the National Cancer Institute (NCI) in the United States to explore molecular alterations in cancer, including uveal melanoma (UM). This led to TCGA classification for UM. In this report, we review the American Joint Committee on Cancer (AJCC) classification and TCGA classification for UM from the NCI\u27s Center for Cancer Genomics (NCI CCG) (based on enucleation specimens [n = 80 eyes]) and from Wills Eye Hospital (WEH) (based on fine needle aspiration biopsy [FNAB] specimens [n = 658 eyes]). We then compare accuracy and predictability of AJCC versus (vs.) TCGA. Methods: Review of published reports on AJCC and TCGA classification for UM was performed. Outcomes based on AJCC 7th and 8th editions were assessed. For TCGA, UM was classified based on chromosomes 3 and 8 findings including disomy 3 (D3), monosomy 3 (M3), disomy 8 (D8), 8q gain (8qG), or 8q gain multiple (8qGm) and combined into four classes including Class A (D3/D8), Class B (D3/8qG), Class C (M3/8qG), and Class D (M3/8qGm). Outcomes of metastasis and death were explored and a comparison (AJCC vs. TCGA) was performed. Results: In the NCI CCG study, there were 80 eyes with UM sampled by enucleation (n = 77), resection (n = 2), or orbitotomy (n = 1) and analysis revealed four distinct genetic classes. Metastasis and death outcomes were subsequently evaluated per class in the WEH study. The WEH study reviewed 658 eyes with UM, sampled by FNAB, and found Class A (n = 342, 52%), B (n = 91, 14%), C (n = 118, 18%), and D (n = 107, 16%). Comparison by increasing class (A vs. B vs. C vs. D) revealed older mean patient age (P \u3c 0.001), worse entering visual acuity (P \u3c 0.001), greater distance from the optic disc (P \u3c 0.001), larger tumor diameter (P \u3c 0.001), and greater tumor thickness (P \u3c 0.001). Regarding outcomes, more advanced TCGA class demonstrated increased 5-year risk for metastasis (4% vs. 20% vs. 33% vs. 63%,P \u3c 0.001) with corresponding increasing hazard ratio (HR) (1.0 vs. 4.1, 10.1, 30.0,P= 0.01 for B vs. A andP \u3c 0.001 for C vs. A and D vs. A) as well as increased 5-year estimated risk for death (1% vs. 0% vs. 9% vs. 23%,P \u3c 0.001) with corresponding increasing HR (1 vs. NA vs. 3.1 vs. 13.7,P= 0.11 for C vs. A andP \u3c 0.001 for D vs. A). Comparison of AJCC to TCGA classification revealed TCGA was superior in prediction of metastasis and death from UM. Conclusion: TCGA classification for UM is simple, accurate, and highly predictive of melanoma-related metastasis and death, more so than the AJCC classification

Analysis of Circadian Rhythm Gene Expression With Reference to Diurnal Pattern of Intraocular Pressure in Mice

Citation: Dalvin LA, Fautsch MP. Analysis of circadian rhythm gene expression with reference to diurnal pattern of intraocular pressure in mice. Invest Ophthalmol Vis Sci. 2015;56:265756: -266356: . DOI:10.1167 PURPOSE. To determine the expression of circadian rhythm clock genes in the iris-ciliary body complex of mice and their association with the diurnal pattern of intraocular pressure (IOP). METHODS. Thirty wild-type C57BL/6 mice were acclimated to a 12-hour light-dark cycle. Intraocular pressure was measured with a rebound tonometer at six time points daily (circadian time [CT] 2, 6, 10, 14, 18, and 22 hours) for five consecutive days. On day 6, mice were euthanized at CT 2, 6, 10, 14, 18, and 22. Eyes were flash-frozen or fixed in 4% phosphate-buffered paraformaldehyde. Total RNA was extracted from the iris-ciliary body complex, and RNA expression of circadian rhythm genes Bmal1, Clock, Cry1, Cry2, Per1, and Per2 was assessed by quantitative real-time PCR. Fixed eyes were paraffin embedded, and immunohistochemistry was performed to localize corresponding proteins (BMAL1, CLOCK, CRY1, CRY2, PER1, and PER2). Linear regression analysis was performed to correlate gene expression with IOP. RESULTS. Intraocular pressure demonstrated a consistent circadian pattern. The clock genes Bmal1, Clock, Cry1, Cry2, Per1, and Per2 showed a circadian pattern of expression in the iris-ciliary body complex of mice. Bmal1, Clock, Cry1, Per1, and Per2 gene expression demonstrated statistically significant correlations with diurnal variations of IOP. BMAL1, CLOCK, CRY1, CRY2, PER1, and PER2 proteins were found to be expressed locally in the nonpigmented epithelium of the ciliary body. CONCLUSIONS. Expression patterns of candidate circadian rhythm genes correlates with the diurnal pattern variation of IOP in mouse eyes, indicating a possible mechanism of IOP regulation through these genes. Keywords: aqueous outflow, iris-ciliary body complex, clock genes, intraocular pressure, circadian rhythm E levated intraocular pressure (IOP) is a strong risk factor for primary open-angle glaucoma (POAG), and current standard of care focuses on the reduction in IOP as the primary modality to reduce optic nerve damage and prevent vision loss. 1 Characterization of molecular regulators of IOP would help identify novel molecules that can be used as therapeutic targets for the treatment of POAG. Intraocular pressure is the result of a balance between secretion and outflow of aqueous humor, a colorless fluid in the anterior segment of the eye. 2 Three variables are of interest in this balance: the rate of aqueous humor formation, the resistance to outflow, and the episcleral venous pressure. The rate of formation and resistance to outflow are the primary targets for current drug therapy aimed at lowering IOP. The ciliary body is responsible for aqueous humor production, primarily via active secretion from its nonpigmented epithelium. Aqueous humor secretion is known to vary in a circadian manner, decreasing by up to 50% during sleep. 8 Epinephrine may play a role in this change, but the mechanism behind decreased secretion remains poorly understood. 9 Outflow facility also decreases slightly at night. 10,11 However, the decrease in outflow does not appear to be significant enough to compensate for the decrease in aqueous secretion, and the cause of this decrease in outflow remains unknown. 10 While the decrease in aqueous humor secretion and the slight decrease in aqueous humor outflow suggest a nocturnal normality or slight decrease in IOP, multiple studies have repeatedly demonstrated a sinusoidal pattern of IOP that peaks at night when animals are maintained on a 12-hour light-dark cycle. 12-16 Interestingly, IOP is higher at night irrespective of diurnal or nocturnal habits of the animals, which suggests that IOP is regulated by light intensity and not by the level of activity. 17 This circadian pattern of IOP is abolished in the absence of a distinct light-dark cycle