Faculty Bibliography

OBJECTIVE: To develop consensus recommendations for reporting of quantitative optical coherence tomography (OCT) study results. METHODS: A panel of experienced OCT researchers (including 11 neurologists, 2 ophthalmologists, and 2 neuroscientists) discussed requirements for performing and reporting quantitative analyses of retinal morphology and developed a list of initial recommendations based on experience and previous studies. The list of recommendations was subsequently revised during several meetings of the coordinating group. RESULTS: We provide a 9-point checklist encompassing aspects deemed relevant when reporting quantitative OCT studies. The areas covered are study protocol, acquisition device, acquisition settings, scanning protocol, funduscopic imaging, postacquisition data selection, postacquisition data analysis, recommended nomenclature, and statistical analysis. CONCLUSIONS: The Advised Protocol for OCT Study Terminology and Elements recommendations include core items to standardize and improve quality of reporting in quantitative OCT studies. The recommendations will make reporting of quantitative OCT studies more consistent and in line with existing standards for reporting research in other biomedical areas. The recommendations originated from expert consensus and thus represent Class IV evidence. They will need to be regularly adjusted according to new insights and practices.

Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide. To identify new susceptibility loci, we performed meta-analysis on genome-wide association study (GWAS) results from eight independent studies from the United States (3,853 cases and 33,480 controls) and investigated the most significantly associated SNPs in two Australian studies (1,252 cases and 2,592 controls), three European studies (875 cases and 4,107 controls) and a Singaporean Chinese study (1,037 cases and 2,543 controls). A meta-analysis of the top SNPs identified three new associated loci: rs35934224[T] in TXNRD2 (odds ratio (OR) = 0.78, P = 4.05 x 10(-11)) encoding a mitochondrial protein required for redox homeostasis; rs7137828[T] in ATXN2 (OR = 1.17, P = 8.73 x 10(-10)); and rs2745572[A] upstream of FOXC1 (OR = 1.17, P = 1.76 x 10(-10)). Using RT-PCR and immunohistochemistry, we show TXNRD2 and ATXN2 expression in retinal ganglion cells and the optic nerve head. These results identify new pathways underlying POAG susceptibility and suggest new targets for preventative therapies.

Visual sensory substitution devices provide a non-surgical and flexible approach to vision rehabilitation in the blind. These devices convert images taken by a camera into cross-modal sensory signals that are presented as a surrogate for direct visual input. While previous work has demonstrated that the visual cortex of blind subjects is recruited during sensory substitution, the cognitive basis of this activation remains incompletely understood. To test the hypothesis that top-down input provides a significant contribution to this activation, we performed functional MRI scanning in 11 blind (7 acquired and 4 congenital) and 11 sighted subjects under two conditions: passive listening of image-encoded soundscapes before sensory substitution training and active interpretation of the same auditory sensory substitution signals after a 10-minute training session. We found that the modulation of visual cortex activity due to active interpretation was significantly stronger in the blind over sighted subjects. In addition, congenitally blind subjects showed stronger task-induced modulation in the visual cortex than acquired blind subjects. In a parallel experiment, we scanned 18 blind (11 acquired and 7 congenital) and 18 sighted subjects at rest to investigate alterations in functional connectivity due to visual deprivation. The results demonstrated that visual cortex connectivity of the blind shifted away from sensory networks and toward known areas of top-down input. Taken together, our data support the model of the brain, including the visual system, as a highly flexible task-based and not sensory-based machine.

The use of ocular imaging tools to estimate structural and functional damage in glaucoma has become a common clinical practice and a substantial focus of vision research. The evolution of the imaging technologies through increased scanning speed, penetration depth, image registration and development of multimodal devices has the potential to detect the pathology more reliably and in earlier stages. This review is focused on new ocular imaging modalities used for glaucoma diagnosis.

Characterizing the collagen fiber orientation and organization in the eye is necessary for a complete understanding of ocular biomechanics. In this study, we assess the performance of polarized light microscopy to determine collagen fiber orientation of ocular tissues. Our results demonstrate that the method provides objective, accurate, repeatable and robust data on fiber orientation with microm-scale resolution over a broad, cm-scale, field of view, unaffected by formalin fixation, without requiring tissue dehydration, labeling or staining. Together, this shows that polarized light microscopy is a powerful method for studying collagen architecture in the eye, with applications ranging from normal physiology and aging, to pathology and transplantation.

AIM: To evaluate outcomes of ab interno trabeculectomy (AIT) with the trabectome following failed trabeculectomy. METHODS: Prospective study of AITs and phaco-AITs after a failed trabeculectomy. The indication for AIT was intraocular pressure (IOP) above target on maximally tolerated therapy, and for phaco-AIT a visually significant cataract and need to lower IOP or glaucoma medications. Outcomes included IOP, medications, complications, secondary procedures and success, defined as IOP of less than 21 mm Hg and a greater than 20% reduction from baseline without further surgery. Exclusion criteria were trabeculectomy less than 3 months prior to AIT or follow-up under 1 year. RESULTS: Seventy-three eyes of 73 patients with 1 year follow-up were identified. At 1 year, mean IOP in AIT significantly decreased by 28% from 23.7+/-5.5 mm Hg, and medications from 2.8+/-1.2 to 2+/-1.3 (n=58). In phaco-AIT, the mean IOP decreased 19% from 20+/-5.9 mm Hg and medications from 2.5+/-1.5 to 1.6+/-1.4 (n=15). Transient hypotony occurred in 7%, and further surgery was necessary in 18%. For AIT and phaco-AIT, the 1-year cumulative probability of success was 81% and 87%, respectively. CONCLUSIONS: Both AIT and phaco-AIT showed a reduction in IOP and medication use after 1 year, suggesting that AIT with or without cataract surgery is a safe and effective option following failed trabeculectomy.

AIM: To analyse ab interno trabeculectomy (AIT) with the trabectome and combined phacoemulsification with AIT (phaco-AIT) by Shaffer angle grade (SG). METHODS: Prospective study of AIT and phaco-AIT with narrow angles of SG/=3. Outcomes included intraocular pressure (IOP), medications, complications, secondary surgery and success (IOP <21 mm Hg and >20% reduction without further surgery). Exclusion criteria were missing preoperative data and <1 year follow-up. RESULTS: Of 671 included cases, at 1 year AIT SG/=3 (n=271) with an IOP reduction of 37% from 26.1+/-7.8 to 16.4+/-3.9 mm Hg (p<0.01). In phaco-AIT with SG/=3 (n=309) with an IOP reduction of 25% from 22.6+/-6.4 to 17.0+/-3.4 mm Hg (p<0.01). There was no difference between SG/=3 in reduction of IOP or medications, complications, secondary surgery and success rates (p>0.05). CONCLUSIONS: SG