Modified-dropless protocol (nil intraocular) for micro-incision vitrectomy surgery (MIVS): a retrospective pilot study.

BACKGROUND: Perioperative infection and inflammation prophylaxis after ocular surgery has evolved over the years along with improvements in surgical equipment and a growing interest in alternatives to the standard topical eye drops. The purpose of this study is to evaluate the outcomes of a novel, modified-dropless protocol for 23-gauge (23-G), 25-gauge (25-G) and 27-gauge (27-G) micro-incision vitrectomy surgery (MIVS) that omits any intraocular injections of antibiotics or steroids. METHODS: This Institutional Review Board-approved, single-surgeon retrospective study reviewed MIVS post-surgical outcomes in patients who received a modified-dropless protocol from February 2020 to March 2021. A total of 158 charts were reviewed, of which 150 eyes met the eligibility criteria. After each case, patients were administered a 0.5 cc subconjunctival injection of a 1:1 Cefazolin (50 mg/cc):Dexamethasone (10 mg/cc) in the inferior fornix and 0.5 cc of posterior Sub-Tenon's Kenalog (STK). No intravitreal injections were administered, and no pre- or postoperative antibiotic or steroid eye drops were prescribed. For patients allergic to penicillin, separate subconjunctival injections of 0.25 cc each of Vancomycin (10 mg/cc) and Dexamethasone (10 mg/cc) were administered. The primary safety parameter was postoperative cases of endophthalmitis. Secondary endpoints consisted of Best-Corrected Distance Visual Acuity (BCVA), intraocular pressure (IOP), and postoperative complications (retinal detachments, inflammation, need for additional surgery) within three months of surgery. Statistical analysis was performed using chi-square (χ²) tests for categorical values, and a Student's t-test to compare continuous outcomes. RESULTS: The majority of surgeries (96%) were performed with the 27G MIVS platform. There were no cases of postoperative endophthalmitis. Mean logMAR BCVA improved from 0.71 (± 0.67) to 0.61 (± 0.60) post-operatively (p = 0.02). Excluding patients who had silicone oil tamponade, postoperative BCVA improved from 0.67 (± 0.66) to 0.54 (± 0.55) (p = 0.003). Mean IOP increased from 14.6 (± 3.8) to 15.3 (± 4.1) (p = 0.05). Ten patients required further medication therapy for an increase in IOP, one had inflammatory signs, and 14 required a second surgical intervention mostly due to recurrences of initial surgical indication. CONCLUSION: A modified-dropless postoperative protocol involving subconjunctival and posterior sub-Tenon's injections only may be a safe and convenient alternative to topical eye drops for patients undergoing MIVS, but additional and larger studies are needed.

A murine RP1 missense mutation causes protein mislocalization and slowly progressive photoreceptor degeneration.

Mutations in the RP1 gene can cause retinitis pigmentosa. We identified a spontaneous L66P mutation caused by two adjacent point mutations in the Rp1 gene in a colony of C57BL/6J mice. Mice homozygous for the L66P mutation exhibited slow, progressive photoreceptor degeneration throughout their lifespan. Optical coherence tomography imaging found abnormal photoreceptor reflectivity at 1 month of age. Histology found shortening and disorganization of the photoreceptor inner and outer segments and progressive thinning of the outer nuclear layer. Electroretinogram a- and b-wave amplitudes were decreased with age. Western blot analysis found that the quantity and size of the mutated retinitis pigmentosa 1 (RP1) protein were normal. However, immunohistochemistry found that the mutant Rp1 protein partially mislocalized to the transition zone of the shortened axonemes. This mutation disrupted colocalization with cytoplasmic microtubules in vitro. In conclusion, the L66P mutation in the first doublecortin domain of the Rp1 gene impairs Rp1 protein localization and function, leading to abnormalities in photoreceptor outer segment structure and progressive photoreceptor degeneration. This is the first missense mutation in Rp1 shown to cause retinal degeneration. It provides a unique, slowly progressive photoreceptor degeneration model that mirrors the slow degeneration kinetics in most patients with retinitis pigmentosa.

Extraocular muscle enlargement leading to the diagnoses of Burkitt lymphoma and acquired immune deficiency syndrome.

Orbital involvement in nonendemic Burkitt lymphoma is rare. The authors report a unique case of a patient who sought treatment for extraocular muscle enlargement without a concurrent orbital mass, which subsequently led to the diagnoses of Burkitt lymphoma and acquired immune deficiency syndrome in an adult patient. The case report adhered to the principles of the Declaration of Helsinki and Health Insurance Portability and Accountability Act compliance. This single case report was institutional review board exempt, given that it does not meet the definition of human subjects' research.

Medical Therapy and Scleral Windows for Uveal Effusion Syndrome: A Case Series and Literature Review.

INTRODUCTION: Uveal effusion syndrome (UES) is a rare ocular disease causing idiopathic uveal effusion, often with associated ciliochoroidal and retinal detachment. UES diagnosis is challenging because of overlapping features with other ocular inflammatory, neoplastic, iatrogenic, and drug-induced causes of uveal effusion. While several successful surgical treatments have been described, such as full-thickness or partial-thickness sclerectomy, medical therapies may also have a therapeutic role. OBJECTIVE: To provide an updated review of the published literature on the course of the disease, medical and surgical management strategies, as well as newer treatment modalities.

Radiation retinopathy intricacies and advances in management.

BACKGROUND: Radiation retinopathy is a chronic, progressive, vision-threatening complication from exposure to various radiation sources. While several treatment modalities are available, proper management for this disease is a continuing challenge with no consensus on the most efficacious. OBJECTIVE: The aim of this article is to provide an updated review of the published literature on the course of the disease, available treatments and their efficacies, frequency of regimen, core issues in patient management, and additional newer treatment modalities, including possible prophylactic approaches. VALUE: We also highlighted the challenges encountered with managing chronically treated patients through an analysis of a clinical case report on a patient who was treated for several years with different modalities after a diagnosis of radiation retinopathy.

Novel Postoperative Dropless Protocol for Micro-Incision Vitrectomy Surgery.

BACKGROUND AND OBJECTIVE: To evaluate the outcomes of a novel postoperative dropless protocol for 25-gauge and 27-gauge micro-incision vitrectomy surgery (MIVS). PATIENTS AND METHODS: The institutional review board approved a single-center, retrospective study. A total of 493 surgeries were identified, and 451 cases from 369 patients met eligibility criteria. Instead of pre- or postoperative drops, patients were given a novel postoperative dropless protocol consisting of subconjunctival injections of a 1:1 cefazolin:dexamethasone mix at each sclerotomy and intravitreally, and injection of posterior sub-Tenon's Kenalog. Primary outcome measure was cases of postoperative endophthalmitis. RESULTS: There was one presumed case of endophthalmitis. Anterior chamber paracentesis sample was negative for culture and Gram stain. For all patients, mean logMAR best-corrected visual acuity improved from 0.65 (±0.69) to 0.57 (±0.61) postoperatively (P = 0.004). Mean intraocular pressure increased from 14.5 (±4.3) to 15.5 (±4.8) postoperatively (P < 0.001). Mean follow-up was 96 days. CONCLUSION: This novel postoperative dropless protocol could potentially be a convenient alternative to topical eye drops for patients undergoing MIVS, but further study is required to establish its safety. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:587-592.].

A Case of Extensive Bilateral Idiopathic Sclerochoroidal Calcification and Review of Literature.

A 62-year-old Caucasian male was referred to retina for choroiditis and uveitis. Multiple areas of yellow irregularities were noted on fundus exam throughout the periphery of both eyes, corresponding to lesions at the sclerochoroidal junction on OCT. A diagnosis of sclerochoroidal calcifications (SCC) was confirmed by B-ultrasonography, fundus photography, OCT imaging, and fluorescein and indocyanine green angiography. Systemic metabolic studies were performed, which showed reduced renal function with increased serum calcium; however, SCC lesions in this case were most likely idiopathic. In this work, we report the clinical findings, appearance on multimodal imaging, and systemic associations of sclerochoroidal calcification. Sclerochoroidal calcifications are an unusual clinical finding that tends to be idiopathic, but a focused workup and specialist referral may be warranted to exclude systemic conditions associated with abnormal calcium-phosphate metabolism or hypokalemic metabolic alkalosis syndromes.

Pathogenesis and Prevention of Worsening Axial Elongation in Pathological Myopia.

PURPOSE: This review discusses the etiology and pathogenesis of myopia, prevention of disease progression and worsening axial elongation, and emerging myopia treatment modalities. INTRODUCTION: Pediatric myopia is a public health concern that impacts young children worldwide and is associated with numerous future ocular diseases such as cataract, glaucoma, retinal detachment and other chorioretinal abnormalities. While the exact mechanism of myopia of the human eye remains obscure, several studies have reported on the role of environmental and genetic factors in the disease development. METHODS: A review of literature was conducted. PubMed and Medline were searched for combinations and derivatives of the keywords including, but not limited to, "pediatric myopia", "axial elongation", "scleral remodeling" or "atropine." The PubMed and Medline database search were performed for randomized control trials, systematic reviews and meta-analyses using the same keyword combinations. RESULTS: Studies have reported that detection of genetic correlations and modification of environmental influences may have a significant impact in myopia progression, axial elongation and future myopic ocular complications. The conventional pharmacotherapy of pediatric myopia addresses the improvement in visual acuity and prevention of amblyopia but does not affect axial elongation or myopia progression. Several studies have published varying treatments, including optical, pharmacological and surgical management, which show great promise for a more precise control of myopia and preservation of ocular health. DISCUSSION: Understanding the role of factors influencing the onset and progression of pediatric myopia will facilitate the development of successful treatments, reduction of disease burden, arrest of progression and improvement in future of the management of myopia.

25 vs. 27-gauge micro-incision vitrectomy surgery for visually significant macular membranes and full-thickness macular holes: a retrospective study.

BACKGROUND: To evaluate visual and safety outcomes for 25-gauge (25G) and 27-gauge (27G) micro-incision vitrectomy platforms (MIVS) for the treatment of epiretinal membrane and full-thickness macular holes. METHODS: Retrospective analysis of all patients who underwent internal limiting membrane (ILM) peel surgery from January 2017 through December 2018. 207 cases met the eligibility criteria for inclusion. Primary endpoint was post-operative Best-Corrected Distance Visual Acuity (BCVA) at 6 months. RESULTS: For all patients combined, mean logMAR BCVA improved from 0.57 (± 0.40) to 0.37 (± 0.36) post-operatively (p < 0.001). For 25G ERMs, logMAR BCVA improved from 0.51 (± 0.28) to 0.30 (± 0.25) post-operatively (p < 0.001). For 27G ERMs, logMAR BCVA improved from 0.33 (± 0.28) to 0.28 (± 0.27) post- operatively (p = 0.15). For 25G FTMHs, logMAR BCVA improved from 0.87 (± 0.48) to 0.51 (± 0.44) post-operatively (p < 0.001). For 27G FTMHs, logMAR BCVA changed from 0.89 (± 0.47) to 0.96 (± 0.60). CONCLUSION: Final visual outcomes improved for both 25G and 27G ERM groups and the 25G FTMH group. Both 25G and 27G were safe and well tolerated MIVS platforms for the treatment of ERM and FTMH.

Unique molecular signatures of microRNAs in ocular fluids and plasma in diabetic retinopathy.

The main objective of this pilot study was to identify circulatory microRNAs in aqueous or plasma that were reflecting changes in vitreous of diabetic retinopathy patients. Aqueous, vitreous and plasma samples were collected from a total of 27 patients undergoing vitreoretinal surgery: 11 controls (macular pucker or macular hole patients) and 16 with diabetes mellitus(DM): DM-Type I with proliferative diabetic retinopathy(PDR) (DMI-PDR), DM Type II with PDR(DMII-PDR) and DM Type II with nonproliferative DR(DMII-NPDR). MicroRNAs were isolated using Qiagen microRNeasy kit, quantified on BioAnalyzer, and profiled on Affymetrix GeneChip miRNA 3.0 microarrays. Data were analyzed using Expression Console, Transcriptome Analysis Console, and Ingenuity Pathway Analysis. The comparison analysis of circulatory microRNAs showed that out of a total of 847 human microRNA probes on the microarrays, common microRNAs present both in aqueous and vitreous were identified, and a large number of unique microRNA, dependent on the DM type and severity of retinopathy. Most of the dysregulated microRNAs in aqueous and vitreous of DM patients were upregulated, while in plasma, they were downregulated. Dysregulation of miRNAs in aqueous did not appear to be a good representative of the miRNA abundance in vitreous, or plasma, although a few potential candidates for common biomarkers stood out: let-7b, miR-320b, miR-762 and miR-4488. Additionally, each of the DR subtypes showed miRNAs that were uniquely dysregulated in each fluid (i.e. aqueous: for DMII-NPDR was miR-455-3p; for DMII-PDR was miR-296, and for DMI-PDR it was miR-3202). Pathway analysis identified TGF-beta and VEGF pathways affected. The comparative profiling of circulatory miRNAs showed that a small number of them displayed differential presence in diabetic retinopathy vs. controls. A pattern is emerging of unique molecular microRNA signatures in bodily fluids of DR subtypes, offering promise for the use of ocular fluids and plasma for diagnostic and therapeutic purposes.

Orally Administered Alpha Lipoic Acid as a Treatment for Geographic Atrophy: A Randomized Clinical Trial.

PURPOSE: Alpha lipoic acid (ALA) is a nutraceutical and potent antioxidant that has shown efficacy in the retina light damage mouse model and in humans for multiple sclerosis. Our objective was to evaluate the efficacy and safety of oral ALA for the treatment of geographic atrophy (GA). DESIGN: Randomized, controlled, double-masked, multicenter phase 2 clinical trial of ALA versus placebo. PARTICIPANTS: Participants with unilateral or bilateral GA from age-related macular degeneration. METHODS: Participants were randomized to 1200 mg daily of ALA or placebo. Fundus autofluorescence, fundus color photography, and spectral-domain OCT were conducted and best-corrected visual acuity (BCVA) was obtained at baseline and every 6 months through month 18. MAIN OUTCOME MEASURES: Annual rate of change over 18 months in square root-transformed area of GA in study eyes as measured on fundus autofluorescence. Secondary outcomes included the number of adverse events (AEs), change in BCVA, and annual rate of change in area of GA measured on color photographs. RESULTS: Fifty-three participants (mean age, 80 years) were randomized (April 2016-August 2017). Twenty-seven participants (37 eyes) were in the placebo group, and 26 participants (36 eyes) were in the ALA group. Unadjusted mean (standard error) annual change in GA area was 0.28 (0.02) mm and 0.31 (0.02) mm for the placebo and ALA groups, respectively (difference, 0.04 mm; 95% confidence interval [CI], -0.03 to 0.11 mm; P = 0.30). Adjusting for baseline GA area, number of GA lesions, and presence of subfoveal GA, the mean annual change in GA area was 0.27 (0.04) mm and 0.32 (0.05) mm for the placebo and ALA groups, respectively (difference, 0.05 mm; 95% CI, -0.02 to 0.12 mm; P = 0.14). At 18 months, the percent of eyes losing 15 letters or more of BCVA was 22% (8 of 36) and 14% (5 of 36) in the placebo and ALA groups, respectively (P = 0.54). No difference was found in the percentage of participants with nonserious AEs (P = 0.96) or serious AEs (P = 0.28) between the placebo and ALA groups. CONCLUSIONS: Results do not support ALA having beneficial effects on GA or BCVA. This trial design may be useful for other GA repurposing drug trials.

Double-Needle Yamane Repositioning of a Previous Yamane Fixation.

We describe a case of anteriorly dislocated, Yamane-fixated secondary intraocular lens (IOLs) with pigmentary dispersion syndrome. The patient presented with significant visual impairment and elevated intraocular pressure despite being maximally treated with all topical antihypertensive medications. The iris-IOL touch was confirmed by ultrasound biomicroscopy, and fundus examination revealed evidence of pigment granules on the optic disc. The previous Yamane-fixated secondary IOL was repositioned using a double-needle adaptation of Yamane technique and Kim's modification of scleral-fixated IOLs. To our knowledge, this is the first ever documented case of double-needle Yamane technique of a previous Yamane-fixated eye. In cases of inadequate capsular support, the development of new surgical techniques for the fixation of IOL continues to improve the safety and efficacy of these complicated surgeries.

GSTM1 and GSTM5 Genetic Polymorphisms and Expression in Age-Related Macular Degeneration.

PURPOSE: Previously, two cytosolic antioxidant enzymes, Glutathione S-transferase Mu 1 (GSTM1) and Mu 5 (GSTM5), were reduced in retinas with age-related macular degeneration (AMD). This study compared genomic copy number variations (gCNV) of these two antioxidant enzymes in AMD versus controls. METHODS: Genomic copy number (gCN) assays were performed using Taqman Gene Copy Number Assays (Applied Biosystems, Darmstadt, Germany) in technical quadruplicate for both GSTM1 and GSTM5. Peripheral leukocyte RNA levels were compared with controls in technical triplicates. Statistical comparisons were performed in SAS v9.2 (SAS Institute Inc., Cary, NC). RESULTS: A large percentage of patients in both AMD and age-matched control groups had no copies of GSTM1 (0/0). The mean gCN of GSTM1 was 1.40 (range 0-4) and 1.61 (range 0-5) for AMD and control, respectively (p = 0.29). A greater percentage of control patients had > 3 gCNs of GSTM1 compared with AMD, respectively (15.3% versus 3.0%, p = 0.004). The gCN of GSTM5 was 2 in all samples except one control sample. The relative quantification of GSTM1 and GSTM5 mRNA from peripheral blood leukocytes in patients showed significant differences in relative expression in AMD versus control (p < 0.05). Peripheral blood leukocyte mRNA and gCN were not significantly correlated (p = 0.27). CONCLUSION: Since high copy numbers of GSTM1 are found more frequently in controls than in AMD, it is possible that high copy number leads to increased retinal antioxidant defense. Genomic polymorphisms of GSTM1 and GSTM5 do not significantly affect the peripheral blood leukocyte mRNA levels.

Improving visual outcomes by preserving outer retina morphology in eyes with resolved pseudophakic cystoid macular edema.

PURPOSE: To use ultra-high-resolution optical coherence tomography (OCT) subclinical anatomic alterations to explain suboptimum vision despite pseudophakic cystoid macula edema (CME) resolution. SETTING: University of California-Davis, Sacramento, California, USA. DESIGN: Case study. METHODS: This study comprised patients who had cataract phacoemulsification surgery. Cases of resolved postoperative CME (diagnosed postoperatively by 1 month and resolved by 1 year) were included. Exclusion criteria included any other cause for decreased vision or compounding factors. Patients with a history of resolved pseudophakic CME were imaged using a purpose-built ultra-high-resolution OCT system with 4.5 µm axial resolution and an acquisition speed of 9 frames/sec (1000 A-scans/frame). The corrected distance visual acuity (CDVA) was determined by Early Treatment Diabetic Retinopathy Study standards. Statistical analysis was by the unpaired t test. A P value less than 0.05 was considered significant. RESULTS: The review identified 56 patients with a pseudophakic CME diagnosis at least 1 month postoperatively. Fifteen eyes (26.8%) had less than 20/20 CDVA despite resolution of CME; 7 participated. Four patients with 20/20 CDVA after resolution of pseudophakic CME participated. Eyes with reduced CDVA after macula edema showed ultra-high-resolution OCT evidence of blurring of outer segments of photoreceptors, while controls showed normal outer retina morphology (P<.05). CONCLUSIONS: Persistent anatomic alteration of photoreceptors visualized by ultra-high-resolution OCT correlated with reduced CDVA in patients with pseudophakic CME compared with patients who had 20/20 CDVA after macula edema. This anatomic alteration in outer photoreceptor morphology is a plausible explanation for the reduced CDVA in this disease. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Landmark matching based retinal image alignment by enforcing sparsity in correspondence matrix.

Retinal image alignment is fundamental to many applications in diagnosis of eye diseases. In this paper, we address the problem of landmark matching based retinal image alignment. We propose a novel landmark matching formulation by enforcing sparsity in the correspondence matrix and offer its solutions based on linear programming. The proposed formulation not only enables a joint estimation of the landmark correspondences and a predefined transformation model but also combines the benefits of the softassign strategy (Chui and Rangarajan, 2003) and the combinatorial optimization of linear programming. We also introduced a set of reinforced self-similarities descriptors which can better characterize local photometric and geometric properties of the retinal image. Theoretical analysis and experimental results with both fundus color images and angiogram images show the superior performances of our algorithms to several state-of-the-art techniques.

Macular edema in the era of spectral-domain optical coherence tomography.

The development of spectral-domain optical coherence tomography (OCT) allows for the highest commercially available resolution of in vivo retinal anatomic details to date. The ability to see the macula with ever increasing detail is dramatically improving our understanding of the pathogenesis of retinal disease. However, the only prospective study that partially evaluated spectral-domain OCT versus time-domain OCT failed to show any clinical benefit of increased OCT resolution. Clinical outcomes, eg, best-corrected visual acuity, central macular thickness and number of injections, with "newer" OCT technologies remain an unproven advantage.

Multimodal assessment of microscopic morphology and retinal function in patients with geographic atrophy.

PURPOSE: To correlate retinal function and visual sensitivity with retinal morphology revealed by ultrahigh-resolution imaging with adaptive optics-optical coherence tomography (AO-OCT), on patients with geographic atrophy. METHODS: Five eyes from five subjects were tested (four with geographic atrophy [66.3 ± 6.4 years, mean ± 1 SD] and one normal [61 years]). Photopic and scotopic multifocal electroretinograms (mfERGs) were recorded. Visual fields were assessed with microperimetry (mP) combined with a scanning laser ophthalmoscope for high-resolution confocal retinal fundus imaging. The eye tracker of the microperimeter identified the preferred retinal locus that was then used as a reference for precise targeting of areas for advanced retinal imaging. Images were obtained with purpose-built, in-house, ultrahigh resolution AO-OCT. Fundus autofluorescence (FAF) and color fundus (CF) photographs were also acquired. RESULTS: The AO-OCT imaging provided detailed cross-sectional structural representation of the retina. Up to 12 retinal layers were identified in the normal subject while many severe retinal abnormalities (i.e., calcified drusen, drusenoid pigment epithelium detachment, outer retinal tubulation) were identified in the retinae of the GA patients. The functional tests showed preservation of sensitivities, although somewhat compromised, at the border of the GA. CONCLUSIONS: The images provided here advance our knowledge of the morphology of retinal layers in GA patients. While there was a strong correlation between altered retinal structure and reduction in visual function, there were a number of examples in which the photoreceptor inner/outer segment (IS/OS) junctions lost reflectivity at the margins of GA, while visual function was still demonstrated. This was shown to be due to changes in photoreceptor orientation near the GA border.

Staging of macular telangiectasia: power-Doppler optical coherence tomography and macular pigment optical density.

PURPOSE: Two methods were used to study the stages of macular telangiectasia (MACTEL): Power-Doppler optical coherence tomography (PD-OCT), which allows imaging of the retinal circulation in three dimensions, and macular pigment optical density (MPOD), which quantifies the distribution of macular carotenoids. METHODS: Among 49 patients with MacTel identified, 12 eyes (6 patients) with MacTel and 7 age-matched control eyes (7 patients) were imaged with a custom-built Fourier-domain OCT instrument to acquire PD-OCT images. MPOD was measured using heterochromatic flicker photometry in 10 eyes (5 patients) with MacTel and compared with 44 age-matched control eyes (44 patients). Clinical staging of MacTel was based on best-corrected visual acuity, fundus biomicroscopy, fluorescein angiography, and OCT. RESULTS: Stage 1 eyes (n = 2) had subtle punctate vascular signal confined to the inner portion of the outer plexiform layer (OPL) on PD-OCT. Stage 2 (n = 2) showed larger oblique vascular signal extending into deeper OPL. Stage 3 (n = 5) had disruption of outer retinal layers with abnormal vasculature extending into the outer nuclear layer. Stage 4 (n = 3) showed diffuse blurring of the retinal layers with vascular channels extending the full thickness of the retina. MPOD values in four eyes with stage 1 or 2 MacTel correlated well with age-matched controls. Six eyes with stage 3 or 4 MacTel had loss of MPOD especially at the fovea. CONCLUSIONS: PD-OCT shows penetration of the retinal capillaries into the deeper retinal layers in early stages of MacTel, with full thickness vascular proliferation in advanced disease. MPOD is commonly depleted but may appear normal in early stage MacTel.

DNA methylation is associated with altered gene expression in AMD.

PURPOSE: Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. Evidence suggests oxidative stress plays a role in the disease. To assess the potential contribution of epigenetic regulation of antioxidant genes relevant to AMD pathogenesis, we evaluated DNA methylation, a tissue-specific genetic modulation that affects gene expression. METHODS: Using the Infinium HumanMethylation27 Illumina platform, we performed DNA bisulfite sequencing to compare the methylation status in postmortem retina pigment epithelium (RPE)/choroid between patients with AMD and age-matched controls. Gene expression was assessed with the Affymetrix Exon Array. TaqMan gene expression assays were used for relative quantification (RT-PCR) confirmation of the expression array results: Glutathione S-transferase isoform mu1 (GSTM1) and mu5 (GSTM5) promoter methylation was confirmed by CpG island bisulfite pyrosequencing. To assess protein levels and localization, we used Western analysis, immunohistochemistry, and immunofluorescence with murine and human samples. RESULTS: The mRNA levels of GSTM1 and GSTM5 were significantly reduced in AMD versus age-matched controls in RPE/choroid and neurosensory retina (NSR), which corresponded to hypermethylation of the GSTM1 promoter. mRNA and protein levels were decreased (RPE to a greater extent than NSR) in AMD postmortem samples, irrespective of age. Immunohistochemistry and immunofluorescence confirm the presence of the enzymes in the NSR and RPE. CONCLUSIONS: Comparison of DNA methylation, together with mRNA levels, revealed significant differences between AMD versus normal retinas. The evidence presented suggests that GSTM1 and GSTM5 undergo epigenetic repression in AMD RPE/choroid, which may increase susceptibility to oxidative stress in AMD retinas.

Landmark matching based automatic retinal image registration with linear programming and self-similarities.

In this paper, we address the problem of landmark matching based retinal image registration. Two major contributions render our registration algorithm distinguished from many previous methods. One is a novel landmark-matching formulation which enables not only a joint estimation of the correspondences and transformation model but also the optimization with linear programming. The other contribution lies in the introduction of a reinforced self-similarities descriptor in characterizing the local appearance of landmarks. Theoretical analysis and a series of preliminary experimental results show both the effectiveness of our optimization scheme and the high differentiating ability of our features.