Publications

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.
Jakobiec F, Rai R, Rashid A, Kanoff J, Mukai S. Dystrophic hyaloid artery remnants and other abnormalities in a buphthalmic eye with retinoblastoma.. Surv Ophthalmol. 2014;59(6):636–642.

Partial persistence of the hyaloid artery unaccompanied by hyperplastic primary vitreous has not been previously reported in association with retinoblastoma. We describe an 18-month-old child with such a finding who had a retinoblastoma that was undifferentiated, extensively necrotic, heavily calcified, and completely filled the eyeball. The enucleated globe harbored a nonperfused, fossilized remnant of the hyaloid artery due to DNA/calcium deposition in the vascular wall. This structure inserted into a lenticular, extracapsular, fibrous plaque corresponding to a Mittendorf dot. The tumor had induced a placoid cataractous lens, obliterated the anterior and posterior chambers, caused glaucoma leading to buphthalmos, and extended into the optic nerve and extraocularly to involve the orbit. We conclude that the retinoblastoma arose early in ocular morphogenesis, at around 4 months gestation, when the programmed involution of the hyaloid artery begins. This process would typically end at 7-8 months gestation, but was aborted by the tumor. The patient died 6 weeks after surgery without receiving further treatment because of the parents' resistance.

Qi Q, Kilpeläinen T, Downer M, Tanaka T, Smith C, Sluijs I, Sonestedt E, Chu A, Renström F, Lin X, Angquist L, Huang J, Liu Z, Li Y, Asif Ali M, Xu M, Ahluwalia TS, Boer J, Chen P, Daimon M, Eriksson J, Perola M, Friedlander Y, Gao YT, Heppe D, Holloway J, Houston D, Kanoni S, Kim YM, Laaksonen M, Jääskeläinen T, Lee N, Lehtimäki T, Lemaitre R, Lu W, Luben R, Manichaikul A, Männistö S, Marques-Vidal P, Monda K, Ngwa J, Perusse L, Rooij F, Xiang YB, Wen W, Wojczynski M, Zhu J, Borecki I, Bouchard C, Cai Q, Cooper C, Dedoussis G, Deloukas P, Ferrucci L, Forouhi N, Hansen T, Christiansen L, Hofman A, Johansson I, Jørgensen T, Karasawa S, Khaw KT, Kim MK, Kristiansson K, Li H, Lin X, Liu Y, Lohman K, Long J, Mikkilä V, Mozaffarian D, North K, Pedersen O, Raitakari O, Rissanen H, Tuomilehto J, Schouw Y, Uitterlinden A, Zillikens C, Franco O, Shyong Tai, Ou Shu X, Siscovick D, Toft U, Verschuren M, Vollenweider P, Wareham N, Witteman J, Zheng W, Ridker P, Kang J, Liang L, Jensen M, Curhan G, Pasquale L, Hunter D, Mohlke K, Uusitupa M, Cupples A, Rankinen T, Orho-Melander M, Wang T, Chasman D, Franks P, Sørensen T, Hu F, Loos R, Nettleton J, Qi L. FTO genetic variants, dietary intake and body mass index: insights from 177 330 individuals.. Hum Mol Genet. 2014;23(25):6961–72.

FTO is the strongest known genetic susceptibility locus for obesity. Experimental studies in animals suggest the potential roles of FTO in regulating food intake. The interactive relation among FTO variants, dietary intake and body mass index (BMI) is complex and results from previous often small-scale studies in humans are highly inconsistent. We performed large-scale analyses based on data from 177 330 adults (154 439 Whites, 5776 African Americans and 17 115 Asians) from 40 studies to examine: (i) the association between the FTO-rs9939609 variant (or a proxy single-nucleotide polymorphism) and total energy and macronutrient intake and (ii) the interaction between the FTO variant and dietary intake on BMI. The minor allele (A-allele) of the FTO-rs9939609 variant was associated with higher BMI in Whites (effect per allele = 0.34 [0.31, 0.37] kg/m(2), P = 1.9 × 10(-105)), and all participants (0.30 [0.30, 0.35] kg/m(2), P = 3.6 × 10(-107)). The BMI-increasing allele of the FTO variant showed a significant association with higher dietary protein intake (effect per allele = 0.08 [0.06, 0.10] %, P = 2.4 × 10(-16)), and relative weak associations with lower total energy intake (-6.4 [-10.1, -2.6] kcal/day, P = 0.001) and lower dietary carbohydrate intake (-0.07 [-0.11, -0.02] %, P = 0.004). The associations with protein (P = 7.5 × 10(-9)) and total energy (P = 0.002) were attenuated but remained significant after adjustment for BMI. We did not find significant interactions between the FTO variant and dietary intake of total energy, protein, carbohydrate or fat on BMI. Our findings suggest a positive association between the BMI-increasing allele of FTO variant and higher dietary protein intake and offer insight into potential link between FTO, dietary protein intake and adiposity.

Sun J, Lin M, Lammer J, Prager S, Sarangi R, Silva P, Aiello LP. Disorganization of the retinal inner layers as a predictor of visual acuity in eyes with center-involved diabetic macular edema.. JAMA Ophthalmol. 2014;132(11):1309–16.

IMPORTANCE: Biomarkers that predict future visual acuity (VA) in eyes with baseline diabetic macular edema (DME) would substantively improve risk assessment, management decisions, and selection of eyes for clinical studies targeting DME. OBJECTIVE: To determine whether baseline or early change in the novel spectral domain-optical coherence tomography (SD-OCT) parameter disorganization of the retinal inner layers (DRIL) is predictive of VA in eyes with center-involved DME. DESIGN, SETTING, AND PARTICIPANTS: At a tertiary care referral center for diabetic eye disease, a retrospective, longitudinal cohort study obtained demographics, VA, and SD-OCT images from baseline, 4-month, and 8-month visits in 96 participants (120 eyes) with diabetes mellitus and baseline center-involved DME (SD-OCT central subfield thickness, ≥ 320 µm for men and ≥ 305 µm for women). Exclusion criteria included substantial media opacity, cataract surgery within 6 months, and nondiabetic retinal pathology affecting VA. On SD-OCT, the 1-mm-wide retinal area centered on the fovea was evaluated by masked graders for DRIL extent, cysts, hyperreflective foci, microaneurysms, cone outer segment tip visibility, and external limiting membrane or photoreceptor disruption and reflectivity. MAIN OUTCOMES AND MEASURES: Visual acuity and SD-OCT-derived retinal morphology. RESULTS: Greater DRIL extent at baseline correlated with worse baseline VA (point estimate, 0.04; 95% CI, 0.02-0.05 per 100 µm; P < .001). An increase in DRIL during 4 months was associated with VA worsening at 8 months (point estimate, 0.03; 95% CI, 0.02-0.05 per 100 µm; P < .001). A multivariate model that included a 4-month change in VA, DRIL, and external limiting membrane disruption was predictive of an 8-month VA change (r = 0.80). Each approximately 300-µm DRIL increase during 4 months predicted a 1-line, 8-month VA decline. When DRIL increased at least 250 µm at 4 months, no eyes had VA improvement of at least 1 line at 8 months. When DRIL decreased at least 250 µm at 4 months, no eyes had VA decline of at least 1 line at 8 months, and 77.7% had VA improvement of at least 1 line. CONCLUSIONS AND RELEVANCE: Disorganization of the retinal inner layers in the 1-mm foveal area is associated with VA, and change in DRIL predicts future change in VA. Early change in DRIL prospectively identifies eyes with a high likelihood of subsequent VA improvement or decline. Therefore, DRIL warrants further study as a robust, readily obtained, and noninvasive biomarker of future VA response in eyes with DME.

Lundgren P, Wilde Å, Löfqvist C, Smith L, Hård AL, Hellström A. Weight at first detection of retinopathy of prematurity predicts disease severity. Br J Ophthalmol. 2014;98(11):1565–9.
OBJECTIVE: To investigate whether postnatal weight at first detection of retinopathy of prematurity (ROP) can predict preterm infants who will develop severe ROP warranting treatment. DESIGN: This modern, population-based cohort included 147 infants born at gestational age (GA) <32 weeks in the Gothenburg region during 2011-2012 and screened for ROP at Sahlgrenska University hospital. GA, birth weight (BW), and weekly postnatal weight from birth until postmenstrual age (PMA) 40 weeks data were retrospectively retrieved. Birth weight SD scores (BWSDS) were calculated. ROP data, including first detected ROP stage, maximal ROP stage, ROP treatment, and PMA at first detected sign of ROP were also retrieved. Weight SDS (WSDS) at first ROP detection was calculated. RESULTS: Stepwise multivariate logistic regression analysis revealed that the best fit-model of risk factors for developing severe ROP warranting treatment included; GA (OR=0.28, CI 95% 0.12 to 0.66, p<0.01) and WSDS at first ROP detection (OR=0.22, CI 95% 0.05 to 0.89, p<0.05). CONCLUSIONS: Low weight and low WSDS at first ROP detection can be useful predictors for ROP warranting treatment.
Yoon M, Piluek WJ, Ruggiero J, McDermott M, McCulley T. Orbital cerebrospinal fluid accumulation after complicated pterional-orbitozygomatic craniotomy.. J Neuroophthalmol. 2014;34(4):346–9.

We describe 2 patients who developed postoperative orbital cerebrospinal fluid (CSF) collection after orbitozygomatic pterional craniotomy. An 18-year-old woman underwent exploratory pterional-orbitozygomatic craniotomy. Five days postoperatively, after removal of a lumbar drain, proptosis and a compressive optic neuropathy developed. Computed tomography demonstrated a CSF collection contiguous with the craniotomy site. Resolution followed percutaneous aspiration and replacement of the lumbar drain. A 57-year-old woman underwent a pterional-orbitozygomatic craniotomy for removal of a left anterior clinoid meningioma, complicated by a large left hemorrhagic stroke requiring decompressive hemicraniectomy. Extracranial CSF collections accumulated in both the orbit and subgaleal spaces. Resolution followed placement of an external ventricular drain. Based on these cases, the mechanism seems to be the combination of iatrogenic formation of a communication with the subarachnoid space and elevated intracranial pressure. Resolution was achieved by normalizing intracranial pressure.