Microperimetric assessment of retinal sensitivity in eyes with diabetic macular edema from a phase 2 study of intravitreal aflibercept.

PURPOSE: To evaluate retinal sensitivity in patients with diabetic macular edema who received intravitreal aflibercept injection (IAI) or laser. METHODS: A substudy included 46 patients from DA VINCI (a randomized, double-masked Phase 2 study) receiving either laser, 0.5 mg IAI every 4 weeks, 2 mg IAI every 4 weeks, 2 mg IAI every 8 weeks after 3 monthly doses (2q8), or 2 mg IAI as-needed after 3 monthly doses for 52 weeks. Retinal sensitivity was measured in one (central), five (one central and four inner), and eight (four inner and four outer) optical coherence tomography subfields. RESULTS: Mean best-corrected visual acuity improvement in the subgroup at Week 52 was 3.3 letters with laser and ranged from 5.4 to 16.3 letters in the IAI groups. Retinal sensitivity of laser patients at Week 52 was comparable with baseline in the central optical coherence tomography subfield but decreased in the five and eight optical coherence tomography subfields. Compared with laser, retinal sensitivity significantly increased with IAI in the 2q8 and pooled IAI groups in the 5 and 8 optical coherence tomography subfields at Week 52 (P < 0.05). CONCLUSION: Intravitreal aflibercept injection improved best-corrected visual acuity and retinal sensitivity in this subgroup of patients. Laser may cause a deterioration of macular function that is not detectable with best-corrected visual acuity testing.

A case for neuroprotection in ophthalmology: developments in translational research.

Cellular aging occurs by the lifelong accumulation of oxidative damage leading to neuronal apoptosis, termed 'neurodegeneration', and the functional deficits of aging. Loss of visual function is one of the most important quality of life measures for older adults. We discuss recent clinical and laboratory advances in the neuroprotective treatment of the aging eye with particular emphasis on the three major ocular neurodegenerative conditions: glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy (DR).

Normative data set identifying properties of the macula across age groups: integration of visual function and retinal structure with microperimetry and spectral-domain optical coherence tomography.

PURPOSE: A normative database of functional and structural parameters of the macula from normal subjects was established to identify reference points for the diagnosis of patients with macular disease using microperimetry and scanning laser ophthalmoscope/spectral-domain optical coherence tomography (SD-OCT). METHODS: This was a community-based, prospective, cross-sectional study of 169 eyes from subjects aged 21 years to 85 years with best-corrected visual acuity of 20/25 or better and without any ocular disease. Full-threshold macular microperimetry combined with the acquisition of structural parameters of the macula with scanning laser ophthalmoscope/SD-OCT was recorded (SD-OCT/scanning laser ophthalmoscope with add-on Microperimetry module; OPKO). Fixation, central, subfield, and mean retinal thickness were acquired together with macular sensitivity function. Thickness and sensitivity as primary outcome measures were mapped and superimposed correlating topographically differentiated macular thickness with sensitivity. Statistical evaluation was performed with age, gender, and ethnicity as covariates. RESULTS: Subfield and mean retinal thickness and sensitivity were measured with macular microperimetry combined with SD-OCT and differentiated by macular topography and subjects' age, gender, and ethnicity. Mean retinal sensitivity and thickness were calculated for 169 healthy eyes (mean age, 48 ± 17 years). A statistically significant decrease in sensitivity was found only in the age group of participants ≥ 70 years and in peripheral portions of the macula in individuals aged ≥60 years and was more pronounced in the area surrounding the fovea than in the center of the macula, while retinal thickness did not change with age. No statistically significant differences in the primary outcome measures or their correlations were found when using gender or ethnicity as a covariate. CONCLUSION: A database for normal macular thickness and sensitivity was generated with a combined microperimetry SD-OCT system as the basis for comparison of outcome parameters in patients with macular abnormality. Mean retinal sensitivity decreased significantly only in the age group of participants ≥ 70 years and in peripheral portions of the macula in individuals aged ≥60 years, with increasing distance from the fovea, while other parameters, their correlations and covariates, were not affected within the normative data set. No relationship was detected between retinal thickness and retinal sensitivity in the healthy macula.

Resident surgical practice patterns for vitreoretinal surgery in ophthalmic training programs in the United States.

PURPOSE: To assess resident surgical experience in vitreoretinal surgery (VRS) in the United States. DESIGN: Anonymous electronic survey over 2 consecutive years. PARTICIPANTS: A total of 287 third-year ophthalmology residents from US residency programs were included. METHODS: To determine the type and amount of surgical experience in VRS. Residents were contacted via e-mail to complete the survey. A series of follow-up e-mails were sent to nonresponders. E-mail correspondence was sent to program directors of the US residency programs to encourage survey participation. An electronic survey instrument (Survey Monkey) was used to distribute the survey and collect the results. Participants were asked about vitrectomy and scleral buckle procedures as primary surgeon and about office procedures (e.g., intravitreal injections and retinal laser procedures). Questions regarding the self-described "comfort" level of the resident and the Accreditation Council for Graduate Medical Education (ACGME) vitreoretinal requirements for ophthalmology were also included. MAIN OUTCOME MEASURES: Vitreoretinal office and surgical procedures. RESULTS: Of the 114 ophthalmology residency programs in the United States, 3 programs declined to participate and 103 of 228 programs (114 programs per year) did not respond to requests during a 2-year period. Of the 287 total respondents, approximately 59.1% had performed vitrectomy and 40.8% had performed a scleral buckle as the primary surgeon. In the survey of office procedures, 96.7% had performed intravitreal injections, 94.8% had performed macular laser therapy, and 99.6% had performed panretinal photocoagulation. In the self-reported resident "comfort" level section, 59% were "fairly comfortable" knowing the theoretic steps for VRS and 55.4% were "fairly satisfied" with VRS training. However, 72% of respondents were unaware of the correct ACGME minimum operative numbers for VRS. CONCLUSIONS: This self-reported electronic survey of third-year residents suggested that VRS experience at ACGME-accredited programs as primary surgeon was suboptimal for surgeries. A modest majority of residents reported comfort and satisfaction with VRS training for surgery, but a majority was satisfied and had adequate experience with office procedures such as intravitreal injection and laser treatment. Unfortunately, the majority of residents were unaware of the actual numeric ACGME VRS requirements for ophthalmology residency programs.

The optic nerve: radiologic, clinical, and pathologic evaluation.

The radiologic investigation of the optic nerve plays an integral part in the diagnostic evaluation of diverse lesions of the optic pathways including inflammatory diseases, vascular disorders and benign and malignant tumors and these radiologic modalities consist principally of CT and MR imaging and, in vascular lesions, MR angiography and conventional angiography. The selection of radiologic studies and their focus is based on the ophthalmologic examination where the ophthalmologist can often determine the suspected location of lesions in the anterior or posterior visual pathways. Furthermore, inspection of the eye, including adnexal structures and funduscopy, provides additional information in the clinical assessment of these patients. With technical advances in the last few years, CT and MR imaging can detect lesions and determine their location and extent with high sensitivity and specificity. This article discusses the radiologic, clinical, and pathologic evaluation of the optic nerve.

Nampt/PBEF/visfatin serum levels: a new biomarker for retinal blood vessel occlusions.

The main objective of the study was to quantify serum levels of nicotinamide phosphoribosyltransferase (Nampt/pre-B-Cell colony-enhancing factor 1/visfatin) in subjects with a history of retinal vascular occlusions (RVOs), disease conditions characterized by pronounced ischemia, and metabolic energy deficits. A case-control study of 18 subjects with a history of RVO as well as six healthy volunteers is presented. Serum Nampt levels were quantified using a commercially available enzyme-linked immunosorbent assay kit. Serum Nampt levels were 79% lower in patients with a history of RVO compared with that in healthy volunteers (P<0.05). There was no statistically significant difference among the types of RVOs, specifically branch retinal vein occlusions (n=7), central retinal vein occlusions (n=5), hemiretinal vein occlusions (n=3), and central retinal artery occlusions (n=3; P=0.69). Further studies are needed to establish the temporal kinetics of Nampt expression and to determine whether Nampt may represent a novel biomarker to identify at-risk populations, or whether it is a druggable target with the potential to ameliorate the long-term complications associated with the condition, ie, macular edema, macular ischemia, neovascularization, and permanent loss of vision.

Clinical application of optical coherence tomography in combination with functional diagnostics: advantages and limitations for diagnosis and assessment of therapy outcome in central serous chorioretinopathy.

PURPOSE: While identifying functional and structural parameters of the retina in central serous chorioretinopathy (CSCR) patients, this study investigated how an optical coherence tomography (OCT)-based diagnosis can be significantly supplemented with functional diagnostic tools and to what degree the determination of disease severity and therapy outcome can benefit from diagnostics complementary to OCT. METHODS: CSCR patients were evaluated prospectively with microperimetry (MP) and spectral domain optical coherence tomography (SD-OCT) to determine retinal sensitivity function and retinal thickness as outcome measures along with measures of visual acuity (VA). Patients received clinical care that involved focal laser photocoagulation or pharmacotherapy targeting inflammation and neovascularization. RESULTS: Correlation of clinical parameters with a focus on functional parameters, VA, and mean retinal sensitivity, as well as on the structural parameter mean retinal thickness, showed that functional measures were similar in diagnostic power. A moderate correlation was found between OCT data and the standard functional assessment of VA; however, a strong correlation between OCT and MP data showed that diagnostic measures cannot always be used interchangeably, but that complementary use is of higher clinical value. CONCLUSION: The study indicates that integrating SD-OCT with MP provides a more complete diagnosis with high clinical relevance for complex, difficult to quantify diseases such as CSCR.

Spectral domain optical coherence tomography findings of acute branch retinal artery occlusion from calcific embolus.

An 82-year-old female presented with sudden painless decrease in vision in the right eye after awakening. She could see the "superior half" of her vision from the right eye only. On examination, best-corrected vision was 20/300 in the right eye and 20/30 in the left eye. The fundus in the right eye revealed recent superotemporal branch retinal artery occlusion (BRAO) with calcified plaque at the disc. Spectral domain optical coherence tomography (OCT) (OTI Ophthalmic Technologies, Inc.), revealed hyperreflectivity and increased thickness of the inner retinal layers of the superior compared to the inferior retina. Imaging at the optic disc revealed the blocked artery containing a highly reflective material. The high reflectivity of the material and underlying optical shadowing could be characterized as calcific emboli.

Spectral Domain Optical Coherence Tomography Findings of Retinal Macroaneurysm.

A 47-year-old healthy male presented to the ophthalmology clinic with complaint of dry eyes. Examination revealed visual acuity 20/20 in both eyes (OU). Anterior segment examination was normal. Fundus examination and fluorescein angiogram findings were consistent with a non-ruptured macroaneurysm. Spectral domain (SD) optical coherence tomography (OCT) (Ophthalmic Technologies, Ontario, Canada) demonstrated a large 215 mu lumen with inferior hyperreflectivity at the area of hemorrhage. There was focal thickening of the retina to encompass the macroaneurysm but no associated retinal edema. The higher resolution afforded by SD OCT may allow more accurate measurement of the size of the aneurysm, making it possible to evaluate prognostically relevant characteristics of the aneurysm such as hemorrhage in the vessel wall or thrombus in the lumen. This may also allow us to possibly intervene earlier in high-risk cases. SD OCT may be of value in management of retinal macroaneurysm.