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2014

Kloek C, Borboli-Gerogiannis S, Chang K, Kuperwaser M, Newman L, Lane AM, Loewenstein J. A broadly applicable surgical teaching method: evaluation of a stepwise introduction to cataract surgery. J Surg Educ. 2014;71(2):169–75.
OBJECTIVE: Although cataract surgery is one of the most commonly performed surgeries in the country, it is a microsurgical procedure that is difficult to learn and to teach. This study aims to assess the effectiveness of a new method for introducing postgraduate year (PGY)-3 ophthalmology residents to cataract surgery. SETTING: Hospital-based ophthalmology residency program. DESIGN: Retrospective cohort study. PARTICIPANTS: PGY-3 and PGY-4 residents of the Harvard Medical School Ophthalmology Residency from graduating years 2010 to 2012. RESULTS: In July 2009, a new method of teaching PGY-3 ophthalmology residents cataract surgery was introduced, which was termed "the stepwise introduction to cataract surgery." This curriculum aimed to train residents to perform steps of cataract surgery by deliberately practicing each of the steps of surgery under a structured curriculum with faculty feedback. Assessment methods included surveys administered to the PGY-4 residents who graduated before the implementation of these measures (n = 7), the residents who participated in the first and second years of the new curriculum (n = 16), faculty who teach PGY-4 residents cataract surgery (n = 8), and review of resident Accreditation Council for Graduate Medical Education surgical logs. Resident survey response rate was 100%. Residents who participated in the new curriculum performed more of each step of cataract surgery in the operating room, spent more time practicing each step of cataract surgery on a cataract surgery simulator during the PGY-3 year, and performed more primary cataract surgeries during the PGY-3 year than those who did not. Faculty survey response rate was 63%. Faculty noted an increase in resident preparedness following implementation of the new curriculum. There was no statistical difference between the precurriculum and postcurriculum groups in the percentage turnover of cataracts for the first 2 cataract surgery rotations of the PGY-4 year of training. CONCLUSIONS: The introduction of cataract surgery to PGY-3 residents in an organized, stepwise manner improved resident preparedness for the PGY-4 year of residency. This surgical teaching method can be easily applied to other surgical specialties.
Srinivasan P, Kim L, Mettu P, Cousins S, Comer G, Izatt J, Farsiu S. Fully automated detection of diabetic macular edema and dry age-related macular degeneration from optical coherence tomography images.. Biomed Opt Express. 2014;5(10):3568–77.

We present a novel fully automated algorithm for the detection of retinal diseases via optical coherence tomography (OCT) imaging. Our algorithm utilizes multiscale histograms of oriented gradient descriptors as feature vectors of a support vector machine based classifier. The spectral domain OCT data sets used for cross-validation consisted of volumetric scans acquired from 45 subjects: 15 normal subjects, 15 patients with dry age-related macular degeneration (AMD), and 15 patients with diabetic macular edema (DME). Our classifier correctly identified 100% of cases with AMD, 100% cases with DME, and 86.67% cases of normal subjects. This algorithm is a potentially impactful tool for the remote diagnosis of ophthalmic diseases.

Ribeiro AG, Rodrigues RAM, Guerreiro AM, Regatieri CVS. A teleophthalmology system for the diagnosis of ocular urgency in remote areas of Brazil. Arq Bras Oftalmol. 2014;77(4):214–8.
PURPOSES: To validate a teleophthalmology mobile system aimed at improving and providing eye urgency screenings in remote and poor area settings in Brazil. The system enables one or more ophthalmologists to remotely examine a patient's condition and submit a decision describing the gravity of the case. If necessary, the patient can be forwarded to a hospital for further consultation. METHODS: A cellphone (Nexus One model, with a 5 megapixel camera) was used to collect data and pictures from 100 randomly selected patients at the Ophthalmology Emergency Room located at the General Hospital of the Federal University of São Paulo (UNIFESP). Data was then sent remotely to an online recording system to be reviewed by an ophthalmologist who provided feedback regarding the state of ocular urgency. RESULTS were then compared to the gold standard diagnosis provided at the hospital. RESULTS: The diagnosis of urgency was given by two ophthalmologists: one in the hospital (gold standard) and one remotely. When we compared both diagnoses we obtained results of 81.94% specificity, 92.85% sensitivity, and 85% accuracy, with a negative predictive value of 96.72%. This work also included a processing time analysis, resulting in an average time of 8.6 min per patient for remote consultations. CONCLUSIONS: This study is the first that has used only a cellphone for diagnosing the urgency of ocular cases. Based on our results, the system can provide a reliable distinction between urgent and non-urgent situations and can offer a viable alternative for the servicing of underprivileged areas. In screening techniques, the most important outcome is to identify urgent cases with a high level of sensitivity and predictive negative value. Thus, our results demonstrate that this tool is robust and we suggest that a major study aimed to verify its efficiency in resource-poor areas should be initiated.
Kwon M, Lu ZL, Miller A, Kazlas M, Hunter D, Bex P. Assessing binocular interaction in amblyopia and its clinical feasibility. PLoS One. 2014;9(6):e100156.
PURPOSE: To measure binocular interaction in amblyopes using a rapid and patient-friendly computer-based method, and to test the feasibility of the assessment in the clinic. METHODS: Binocular interaction was assessed in subjects with strabismic amblyopia (n = 7), anisometropic amblyopia (n = 6), strabismus without amblyopia (n = 15) and normal vision (n = 40). Binocular interaction was measured with a dichoptic phase matching task in which subjects matched the position of a binocular probe to the cyclopean perceived phase of a dichoptic pair of gratings whose contrast ratios were systematically varied. The resulting effective contrast ratio of the weak eye was taken as an indicator of interocular imbalance. Testing was performed in an ophthalmology clinic under 8 mins. We examined the relationships between our binocular interaction measure and standard clinical measures indicating abnormal binocularity such as interocular acuity difference and stereoacuity. The test-retest reliability of the testing method was also evaluated. RESULTS: Compared to normally-sighted controls, amblyopes exhibited significantly reduced effective contrast (∼20%) of the weak eye, suggesting a higher contrast requirement for the amblyopic eye compared to the fellow eye. We found that the effective contrast ratio of the weak eye covaried with standard clincal measures of binocular vision. Our results showed that there was a high correlation between the 1st and 2nd measurements (r = 0.94, p<0.001) but without any significant bias between the two. CONCLUSIONS: Our findings demonstrate that abnormal binocular interaction can be reliably captured by measuring the effective contrast ratio of the weak eye and quantitative assessment of binocular interaction is a quick and simple test that can be performed in the clinic. We believe that reliable and timely assessment of deficits in a binocular interaction may improve detection and treatment of amblyopia.
Yao J, Ko CW, Baranov P, Regatieri C, Redenti S, Tucker B, Mighty J, Tao S, Young M. Enhanced differentiation and delivery of mouse retinal progenitor cells using a micropatterned biodegradable thin-film polycaprolactone scaffold.. Tissue Eng Part A. 2014;

The deterioration of retinal tissue in advanced stages of retinitis pigmentosa and age-related macular degeneration and the lack of signaling cues for laminar regeneration are significant challenges highlighting the need for a tissue-engineering approach to retinal repair. In this study, we fabricated a biodegradable thin-film polycaprolactone (PCL) scaffold with varying surface topographies using microfabrication techniques. Mouse retinal progenitor cells (mRPC) cultured on PCL scaffolds exhibited enhanced potential to differentiate towards a photoreceptor fate in comparison to mRPCs cultured on control substrates, suggesting that PCL scaffolds are promising as substrates to guide differentiation of mRPCs towards a photoreceptor fate in vitro prior to transplantation. When co-cultured with the retinal explants of rhodopsin null mice, mRPC/PCL constructs showed increased mRPC integration rates compared to directly applied dissociated mRPCs. Moreover, these mRPC/PCL constructs could be delivered into the sub-retinal space of rhodopsin null mice with minimal disturbance of the host retina. Whether co-cultured with retinal explants or transplanted into the sub-retinal space, newly integrated mRPCs localized to the outer nuclear layer and expressed appropriate markers of photoreceptor fate. Thus, the PCL scaffold provides a platform to guide differentiation and organized deliver of mRPCs as a practical strategy to repair damaged retina.

Davies E, Jakobiec F, Stagner A, Iwamoto M. A Rapidly Enlarging Recurrent Eyebrow Pilomatrixoma in a Nonagenarian.. Ophthal Plast Reconstr Surg. 2014;

A rapidly growing, large (horizontal diameter of 3.1 cm) eyebrow lesion in a nonagenarian patient was found on pathologic examination to demonstrate an admixture of islands of anucleated, washed out eosinophilic "ghost" cells with surrounding nucleated, small germinal basaloid cells. Further analysis disclosed adipophilin granular positivity in the necrotic zones, negative nuclear staining for androgen receptor and strong nuclear positivity for Ki67 in the basaloid cells (proliferation index of 50%). These findings are consistent with a highly mitotically active pilomatrixoma. The lesion recurred after initial resection but returned the same histopathologic features as the primary. Several clinical features were notably atypical for pilomatrixoma-specifically, the age of the patient, rapid lesion growth and recurrence, and clinical appearance and large size of the mass. The immunohistochemical findings can help to distinguish this tumor from other skin neoplasms, especially sebaceous carcinoma in an older individual.

Sümbül U, Zlateski A, Vishwanathan A, Masland R, Seung S. Automated computation of arbor densities: a step toward identifying neuronal cell types. Front Neuroanat. 2014;8:139.
The shape and position of a neuron convey information regarding its molecular and functional identity. The identification of cell types from structure, a classic method, relies on the time-consuming step of arbor tracing. However, as genetic tools and imaging methods make data-driven approaches to neuronal circuit analysis feasible, the need for automated processing increases. Here, we first establish that mouse retinal ganglion cell types can be as precise about distributing their arbor volumes across the inner plexiform layer as they are about distributing the skeletons of the arbors. Then, we describe an automated approach to computing the spatial distribution of the dendritic arbors, or arbor density, with respect to a global depth coordinate based on this observation. Our method involves three-dimensional reconstruction of neuronal arbors by a supervised machine learning algorithm, post-processing of the enhanced stacks to remove somata and isolate the neuron of interest, and registration of neurons to each other using automatically detected arbors of the starburst amacrine interneurons as fiducial markers. In principle, this method could be generalizable to other structures of the CNS, provided that they allow sparse labeling of the cells and contain a reliable axis of spatial reference.
Dagi L, Tiedemann L, Heidary G, Robson C, Hall A, Zurakowski D. Using spectral-domain optical coherence tomography to detect optic neuropathy in patients with craniosynostosis.. J AAPOS. 2014;18(6):543–9.

BACKGROUND: Detecting and monitoring optic neuropathy in patients with craniosynostosis is a clinical challenge due to limited cooperation, and subjective measures of visual function. The purpose of this study was to appraise the correlation of peripapillary retinal nerve fiber layer (RNFL) thickness measured by spectral-domain ocular coherence tomography (SD-OCT) with indication of optic neuropathy based on fundus examination. METHODS: The medical records of all patients with craniosynostosis presenting for ophthalmic evaluation during 2013 were retrospectively reviewed. The following data were abstracted from the record: diagnosis, historical evidence of elevated intracranial pressure, current ophthalmic evaluation and visual field results, and current peripapillary RNFL thickness. RESULTS: A total of 54 patients were included (mean age, 10.6 years [range, 2.4-33.8 years]). Thirteen (24%) had evidence of optic neuropathy based on current fundus examination. Of these, 10 (77%) demonstrated either peripapillary RNFL elevation and papilledema or depression with optic atrophy. Sensitivity for detecting optic atrophy was 88%; for papilledema, 60%; and for either form of optic neuropathy, 77%. Specificity was 94%, 90%, and 83%, respectively. Kappa agreement was substantial for optic atrophy (κ = 0.73) and moderate for papilledema (κ = 0.39) and for either form of optic neuropathy (κ = 0.54). Logistic regression indicated that peripapillary RNFL thickness was predictive of optic neuropathy (P < 0.001). Multivariable analysis demonstrated that RNFL thickness measurements were more sensitive at detecting optic neuropathy than visual field testing (likelihood ratio = 10.02; P = 0.002). Sensitivity and specificity of logMAR visual acuity in detecting optic neuropathy were 15% and 95%, respectively. CONCLUSIONS: Peripapillary RNFL thickness measured by SD-OCT provides adjunctive evidence for identifying optic neuropathy in patients with craniosynostosis and appears more sensitive at detecting optic atrophy than papilledema.

Wiecek E, Dakin S, Bex P. Metamorphopsia and letter recognition.. J Vis. 2014;14(14).

Acuity is the most commonly used measure of visual function, and reductions in acuity are associated with most eye diseases. Metamorphopsia-a perceived distortion of visual space-is another common symptom of visual impairment and is currently assessed qualitatively using Amsler (1953) charts. In order to quantify the impact of metamorphopsia on acuity, we measured the effect of physical spatial distortion on letter recognition. Following earlier work showing that letter recognition is tuned to specific spatial frequency (SF) channels, we hypothesized that the effect of distortion might depend on the spatial scale of visual distortion just as it depends on the spatial scale of masking noise. Six normally sighted observers completed a 26 alternate forced choice (AFC) Sloan letter identification task at five different viewing distances, and the letters underwent different levels of spatial distortion. Distortion was controlled using spatially band-pass filtered noise that spatially remapped pixel locations. Noise was varied over five spatial frequencies and five magnitudes. Performance was modeled with logistic regression and worsened linearly with increasing distortion magnitude and decreasing letter size. We found that retinal SF affects distortion at midrange frequencies and can be explained with the tuning of a basic contrast sensitivity function, while object-centered distortion SF follows a similar pattern of letter object recognition sensitivity and is tuned to approximately three cycles per letter (CPL). The interaction between letter size and distortion makes acuity an unreliable outcome for metamorphopsia assessment.