Controlling a Digital Cursor With a Sterile Gyroscopic Mouse in Digitally Assisted Vitreoretinal Surgery.

PURPOSE: To describe our experience using the gyroscopic mouse in digitally assisted vitreoretinal surgery. METHODS: We used a commercially available gyroscopic mouse to control the on-screen cursor of the NGENUITY System for digitally assisted vitreoretinal surgery. The gyroscopic mouse is sealed in a clear sterile plastic bag to allow for intraoperative use. This allowed both the surgeon and assistant to be fully scrubbed while retaining full control of the NGENUITY system's functions. The mouse also allowed the mentor to provide detailed instructions through the on-screen cursor by highlighting important landmarks. CONCLUSION: Using a sterile gyroscopic mouse improved the teaching utility and surgical workflow of digitally assisted vitreoretinal surgery.

Subthreshold Nanosecond Laser Intervention in Age-Related Macular Degeneration: The LEAD Randomized Controlled Clinical Trial.

PURPOSE: There is an urgent need for a more effective intervention to slow or prevent progression of age-related macular degeneration (AMD) from its early stages to vision-threatening late complications. Subthreshold nanosecond laser (SNL) treatment has shown promise in preclinical studies and a pilot study in intermediate AMD (iAMD) as a potential treatment. We aimed to evaluate the safety of SNL treatment in iAMD and its efficacy for slowing progression to late AMD. DESIGN: The Laser Intervention in Early Stages of Age-Related Macular Degeneration (LEAD) study is a 36-month, multicenter, randomized, sham-controlled trial. PARTICIPANTS: Two hundred ninety-two participants with bilateral large drusen and without OCT signs of atrophy. METHODS: Participants were assigned randomly to receive Retinal Rejuvenation Therapy (2RT®; Ellex Pty Ltd, Adelaide, Australia) SNL or sham treatment to the study eye at 6-monthly intervals. MAIN OUTCOME MEASURES: The primary efficacy outcome was the time to development of late AMD defined by multimodal imaging (MMI). Safety was assessed by adverse events. RESULTS: Overall, progression to late AMD was not slowed significantly with SNL treatment compared with sham treatment (adjusted hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.33-1.14; P = 0.122). However, a post hoc analysis showed evidence of effect modification based on the coexistence of reticular pseudodrusen (RPD; adjusted interaction P = 0.002), where progression was slowed for the 222 participants (76.0%) without coexistent RPD at baseline (adjusted HR, 0.23; 95% CI, 0.09-0.59; P = 0.002), whereas an increased progression rate (adjusted HR, 2.56; 95% CI, 0.80-8.18; P = 0.112) was observed for the 70 participants (24.0%) with RPD with SNL treatment. Differences between the groups in serious adverse events were not significant. CONCLUSIONS: In participants with iAMD without MMI-detected signs of late AMD, no significant difference in the overall progression rate to late AMD between those receiving SNL and sham treatment were observed. However, SNL treatment may have a role in slowing progression for those without coexistent RPD and may be inappropriate in those with RPD, warranting caution when considering treatment in clinical phenotypes with RPD. Our findings provide compelling evidence for further trials of the 2RT® laser, but they should not be extrapolated to other short-pulse lasers.

Change in vision after retinal pigment epithelium tear following the use of anti-VEGF therapy for age-related macular degeneration.

PURPOSE: We investigated visual acuity outcomes and their associations in the setting of retinal pigment epithelium tear (RPET) following the use of anti-vascular endothelial growth factor (anti-VEGF) agents. METHODS: This retrospective review included all patients treated for neovascular age-related macular degeneration (AMD) with an anti-VEGF agent who subsequently developed an RPET. All patients who developed an RPET were identified and outcome measures data were recorded and analysed. The main outcome measures were best corrected visual acuity (BCVA) and spectral domain optical coherence tomography characteristics. RESULTS: Among the 14 participants identified, a subfoveal RPET was associated with the loss of one or more lines of vision from baseline (p = 0.03). There was no association between the size of the RPET and BCVA at the time of the RPET or final BCVA. The development of a disciform scar was associated both with a BCVA at the time of the RPET of < 6/24 (p = 0.02) and a final BCVA of < 6/24 (p = 0.02). Ongoing treatment with an anti-VEGF agent following an RPET saw five patients (35.7 %) have an improvement in their BCVA and all patients maintained their BCVA following the RPET with ongoing anti-VEGF treatment. CONCLUSIONS: Visual decline following an RPET is associated with subfoveal location of the RPET (p = 0.03) and later development of a disciform scar. These data also suggest that the ongoing use of an anti-VEGF agent may stabilise vision in some patients following an RPET and for some patients there may be an improvement in visual acuity despite the RPET, depending on its location.

Biochemical analysis of the living human vitreous.

BACKGROUND: To date, our understanding of the biochemical composition of the living human vitreous relies on extrapolations from animal or human post-mortem studies. METHODS: This was a cross-sectional study of vitreous samples from 27 individuals scheduled for retinal surgery within a tertiary hospital. From each vitreous sample, the concentrations of sodium, potassium, chloride, calcium, magnesium, glucose, lactate, ß- hydroxybutyrate, copper, zinc, selenium, iron, ferritin and transferrin and osmolality were measured. Perioperative serum samples were also obtained for comparison. RESULTS: The following vitreous mean ± standard deviation (95% confidence interval of the mean) was observed for each analyte: sodium, 146.7 ± 3.3 (145.4-148.0) mmol/L; potassium, 5.73 ± 0.86 (5.39-6.08) mmol/L; chloride, 121.6 ± 2.6 (120.6-122.7) mmol/L; calcium, 1.128 ± 0.518 (0.923-1.333) mmol/L; magnesium, 0.900 ± 0.158 (0.838-0.962) mmol/L; glucose, 2.97 ± 0.98 (2.58-3.36) mmol/L; lactate, 3.97 ± 1.09 (3.54-4.40) mmol/L; osmolality, 289.5 ± 6.9 (286.6-292.5) mOsm/kg; BOHB, 0.0937 ± 0.0472 (0.0750-0.1124) mmol/L; copper, 0.519 ± 0.269 (0.412-0.625) µmol/L; zinc, 1.95 ± 1.09 (1.52-2.38) µmol/L; selenium, 0.1035 ± 0.0276 (0.0923-0.1146) µmol/L; iron, 3.11 ± 1.40 (2.56-3.66) µmol/L; ferritin, 19.5 ± 10.3 (15.5-23.6) µg/L; transferrin, 0.0878 ± 0.0526 (0.0670-0.1086) g/L. Vitreous biochemistry was not significantly different between male and female participants. Vitreous biochemistry was significantly different between non-diabetic and diabetic participants. Vitreous biochemistry was significantly different from the vitreous substitute BSS Plus (Alcon, USA). The vitreous extracted from living humans was markedly different from the commonly reported reference values obtained from animal studies. CONCLUSIONS: The current data provide hitherto unavailable information about the biochemical composition of the living human vitreous.

Survey of Trachoma within school students in the state of Roraima, Brazil.

PURPOSE: Trachoma, a blinding conjunctivitis, is the result of repeated infection with Chlamydia trachomatis. There are no recent data for the state of Roraima, Brazil, where it was thought that trachoma no longer existed. These data are derived from school children sampled in this state, with additional data collected from the contacts of children with trachoma. DESIGN: A population-based cross-sectional study with random sampling of students in grades 1 through 4 of all public schools within municipalities where the human development index was less than the national average in 2003. The sample was stratified according to population size. PARTICIPANTS: A sample size of 7200 was determined and a total of 6986 (93%) students were examined, along with an additional 2152 contacts. METHODS: All students were examined for trachoma according to World Health Organization criteria. Demographic data and contact information also was collected. The family and school contacts of students with trachoma then were located and examined. MAIN OUTCOME MEASURES: Prevalence and grade of trachoma, age, gender, race, and municipality location. RESULTS: The overall prevalence of trachoma was 4.5% (95% confidence interval [CI], 3.7%-5.3%), but there were municipalities within the state where the prevalence of inflammatory trachoma was more than 10%. The prevalence was greater in rural areas (4.9%; 95% CI, 3.7%-6.0%) compared with urban areas (3.9%; 95% CI, 2.9%-4.9%). Living in indigenous communities was associated with trachoma (odds ratio, 1.6; 95% CI, 0.9-2.6). An additional 2152 contacts were examined, and the overall trachoma prevalence was 9.3% (95% CI, 8.1-10.5). CONCLUSIONS: Trachoma continues to exist in Roraima, Brazil, where there are municipalities with a significant prevalence of disease. The indigenous population is highly mobile, crossing state and international borders, raising the possibility of trachoma in neighboring countries. Trachoma prevalence among the contacts of students with trachoma was higher than the school population, highlighting the importance of contact tracing. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Multimodal Retinal Imaging and Microperimetry Reveal a Novel Phenotype and Potential Trial End Points in CRB1-Associated Retinopathies.

Purpose: Biallelic crumbs cell polarity complex component 1 (CRB1) mutations can present as Leber congenital amaurosis (LCA), retinitis pigmentosa (RP), or cystic maculopathy. This study reports a novel phenotype of asymptomatic fenestrated slit maculopathy (AFSM) and examines macular volume profile and microperimetry as clinical trial end points in CRB1-associated retinopathies. Methods: Twelve patients from nine families with CRB1 mutation were recruited. Ultra-widefield (UWF) color fundus photography and autofluorescence (AF), spectral-domain optical coherence tomography (SD-OCT), microperimetry, and adaptive optics (AO) imaging were performed. Macular volume profiles were compared with age-matched healthy controls. Genotyping was performed using APEX genotyping microarrays, targeted next-generation sequencing, and Sanger sequencing. Results: We identified one patient with LCA, five patients with RP, and four patients with macular dystrophy (MD) with biallelic CRB1 mutations. Two siblings with compound heterozygote genotype (c.[2843G>A]; [498_506del]) had AFSM characterized by localized outer retinal disruption on SD-OCT and parafoveal cone loss on AO imaging despite normal fundus appearance, visual acuity, and foveal sensitivity. UWF AF demonstrated preserved para-arteriolar retinal pigment epithelium (PPRPE) in all patients with RP. Microperimetry documented preserved central retinal function in six patients. The ratio of perifoveal-to-foveal retinal volume was greater than controls in 89% (8/9) of patients with RP or MD, whereas central subfield and total macular volume were outside normal limits in 67% (6/9). Conclusions: AO imaging was helpful in detecting parafoveal cone loss in asymptomatic patients. Macular volume profile and microperimetry parameters may have utility as CRB1 trials end points. Translational Relevance: Macular volume and sensitivity can be used as structural and functional end points for trials on CRB1-associated RP and MD.

A novel syndrome of paediatric cataract, dysmorphism, ectodermal features, and developmental delay in Australian Aboriginal family maps to 1p35.3-p36.32.

BACKGROUND: A novel phenotype consisting of cataract, mental retardation, erythematous skin rash and facial dysmorphism was recently described in an extended pedigree of Australian Aboriginal descent. Large scale chromosomal re-arrangements had previously been ruled out. We have conducted a genome-wide scan to map the linkage region in this family. METHODS: Genome-wide linkage analysis using Single Nucleotide Polymorphism (SNP) markers on the Affymetrix 10K SNP array was conducted and analysed using MERLIN. Three positional candidate genes (ZBTB17, EPHA2 and EPHB2) were sequenced to screen for segregating mutations. RESULTS: Under a fully penetrant, dominant model, the locus for this unique phenotype was mapped to chromosome 1p35.3-p36.32 with a maximum LOD score of 2.41. The critical region spans 48.7 cM between markers rs966321 and rs1441834 and encompasses 527 transcripts from 364 annotated genes. No coding mutations were identified in three positional candidate genes EPHA2, EPHB2 or ZBTB17. The region overlaps with a previously reported region for Volkmann cataract and the phenotype has similarity to that reported for 1p36 monosomy. CONCLUSIONS: The gene for this syndrome is located in a 25.6 Mb region on 1p35.3-p36.32. The known cataract gene in this region (EPHA2) does not harbour mutations in this family, suggesting that at least one additional gene for cataract is present in this region.

Prospective Longitudinal Evaluation of Nascent Geographic Atrophy in Age-Related Macular Degeneration.

PURPOSE: Nascent geographic atrophy (nGA) describes features on OCT imaging previously observed to precede the development of atrophy. This study sought to prospectively evaluate the predictive ability of nGA for the conventional clinical endpoint of geographic atrophy (GA) as defined on color fundus photography (CFP). DESIGN: Prospective, longitudinal, observational study. PARTICIPANTS: A total of 284 eyes from 142 participants with bilateral large drusen and without nGA nor late age-related macular degeneration (AMD) at baseline were included. METHODS: OCT volume scans and CFP images were obtained from all participants at baseline and then at 6-month intervals for up to 36 months. OCT and CFP images were graded independently for the presence of nGA and GA, respectively. Eyes that developed neovascular AMD were censored at the day of its detection. MAIN OUTCOME MEASURES: Time to development of GA. RESULTS: A total 12 eyes from 10 participants progressed to GA over 36 months of follow-up, and nGA was detected in 10 of these eyes (83%) at a preceding visit (median, 13 months prior; interquartile range, 6-25 months). A total of 40 eyes from 28 participants developed nGA or GA over 36 months of follow-up, and the probability of progression to nGA and GA after 36 months was 20% (95% confidence interval [CI], 14%-28%) and 9% (95% CI, 6%-13%), respectively. After the detection of nGA, the probability of progression to GA was 38% (95% CI, 15%-55%) after 24 months. The development of nGA was associated with a markedly increased risk of progression to GA compared with when it did not develop (adjusted hazard ratio, 78.1; 95% CI, 13.6-448.0; P < 0.001), and the development of nGA explained 91% of the variance in the time to GA development. CONCLUSIONS: This study prospectively demonstrated that nGA was a strong predictor for the development of GA, providing supportive evidence of the potential value of nGA as a surrogate endpoint in future intervention trials for the early stages of AMD to improve their feasibility substantially.

A novel genetic syndrome characterized by pediatric cataract, dysmorphism, ectodermal features, and developmental delay in an indigenous Australian family.

A novel syndrome initially presenting with cataract and developmental delay within an Indigenous Australian family is described. We present the extended four generation pedigree and describe in detail the phenotypic appearance of five clearly affected male second cousins in this family. The common features of these children include developmental delay, short stature, cortical cataract, facial dysmorphism, clinodactyly, thin hair and an erythematous skin rash. Initial inspection of the pedigree suggested an inherited disorder with possible X-linked inheritance. However, a thorough scan of the X chromosome failed to reveal linkage. This family represents a new syndrome of familial cataract, dysmorphic features, short stature and developmental delay with probable autosomal inheritance and variable expressivity.

Prevalence and causes of visual impairment in a Brazilian population: the Botucatu Eye Study.

BACKGROUND: This paper reports population-based data on the prevalence and causes of visual impairment among children and adults in Botucatu, Brazil. METHODS: A population-based cross-sectional study was conducted involving a random start point and then systematic sampling of an urban Brazilian population in the city of Botucatu. There were approximately 3,300 individuals aged 1 to 91 years who were eligible to participate in the study. Of this sample, 2485 (75.3%) underwent ophthalmic examination. The ophthalmic examination included uncorrected (presenting) and best corrected distance visual acuity using standardized protocols. The primary cause of decreased visual acuity was identified for all patients with visual impairment. RESULTS: Presenting low vision and presenting blindness were found in 5.2% (95% CI: 4.3-6.1) and 2.2% (95% CI: 1.6-2.8) of the population, respectively. Unilateral presenting low vision and unilateral presenting blindness were found in 8.3% (95% CI: 7.2-9.5) and 3.7% (95% CI: 2.9-4.4) of the population respectively. Best corrected low vision was found in 1.3% of the population (95% CI: 0.9-1.7) and best corrected blindness was discovered in 0.4% of people (95% CI: 0.2-0.7). The main cause of presenting low vision was refractive error (72.3%) and cataract was the most prevalent cause of blindness (50%). CONCLUSION: The main causes of low vision and blindness in this Brazilian city were uncorrected refractive errors, cataract, and retinal diseases. Programs to further reduce the burden of visual impairment need to be targeted toward the correction of refractive error and surgery for cataracts.

Secondary and Exploratory Outcomes of the Subthreshold Nanosecond Laser Intervention Randomized Trial in Age-Related Macular Degeneration: A LEAD Study Report.

PURPOSE: To evaluate the secondary and exploratory outcomes of the Laser Intervention in Early Stages of Age-Related Macular Degeneration (LEAD) study, a 36-month trial of a subthreshold nanosecond laser (SNL) treatment for slowing the progression to late age-related macular degeneration (AMD) in its early stages. DESIGN: Multicenter, randomized, sham-controlled trial. PARTICIPANTS: Two-hundred ninety-two patients with bilateral large drusen. METHODS: Participants were randomly assigned to receive SNL or sham treatment to the study eye at 6-month intervals. MAIN OUTCOME MEASURES: The secondary outcome measure of the LEAD study was the time to development of late AMD, defined by multimodal imaging in the non-study eye. The exploratory outcome measures were the rate of change in best-corrected visual acuity (BCVA), low-luminance visual acuity, microperimetric mean sensitivity, drusen volume in the study and non-study eyes, and participant-reported outcomes based on the Night Vision Questionnaire and Impact of Vision Impairment questionnaire. RESULTS: Progression to late AMD in the non-study eye was not significantly delayed with SNL treatment (hazard ratio, 0.83; 95% confidence interval, 0.40-1.71; P = 0.611). There was no evidence of effect modification based on the coexistence of reticular pseudodrusen; interaction P = 0.065). There was no significant difference between study groups in the rate of change of low-luminance visual acuity, microperimetric mean sensitivity, and drusen volume in the study or non-study eyes, and Night Vision Questionnaire and Impact of Vision Impairment questionnaire scores (all P ≥ 0.167). The rate of BCVA decline was slightly higher for participants in the SNL group compared with the sham treatment group in the study eye (-0.54 and 0.23 letters/year, respectively; P < 0.001) but not the non-study eye (-0.48 and -0.56 letters/year, respectively; P = 0.628). CONCLUSIONS: Subthreshold nanosecond laser treatment of one eye did not have an effect on delaying progression to late AMD in the fellow eye and did not, in general, have an impact on the exploratory structural, functional, and participant-reported outcomes.

Ethmoidal pneumocele following drainage of an ethmoidal mucocele.

Ethmoidal pneumocele is a rare condition with little known about its etiology. We report a 5-year-old boy who had recurrent right orbital cellulitis, non-axial proptosis, and inferolateral globe displacement. Initial radiological investigations demonstrated an ethmoidal mucocele. There was complete resolution of inflammatory signs with endoscopic drainage of the mucocele; however, repeat CT revealed a residual pneumocele with continued proptosis and lateral displacement of the globe. This case illustrates the potential for chronic sinusitis and iatrogenic drainage of an ethmoidal mucocele to progress to a pneumocele.

Eye health programs within remote Aboriginal communities in Australia: a review of the literature.

OBJECTIVE: To review the literature regarding the most sustainable and culturally appropriate ways in which to implement eye health care programs within remote Aboriginal communities in Australia from a primary health care perspective. DATA SOURCES: The search included letters, editorials and papers (published and unpublished) from January 1955 to April 2006. STUDY SELECTION: The search revealed 1,106,758 papers, books and other related material. The relevancy of this material was determined by abstract and 378 relevant articles were reviewed in their entirety. After reading the relevant articles and the interview transcripts the themes that emerged from each source were extracted. CONCLUSIONS: The ten areas to consider include: clinical practice and access, sustainability, regional-based programs, information technology systems, health worker training, self-determination, cultural and language barriers, funding body responsibilities, embedding specialist programs in primary care services, and other considerations. Further research needs to be undertaken within Aboriginal communities in the area of primary eye health care and barriers to the acceptance of treatment. This may be undertaken using more interactive research methods such as cooperative and narrative inquiry.

Prevalence of trachoma-related trichiasis and corneal opacity in rural Myanmar: the Meiktila Eye Study.

OBJECTIVE: To describe the prevalence of trachomatous trichiasis and corneal opacity (CO) within central Myanmar. DESIGN: Population-based cross-sectional ophthalmic survey. PARTICIPANTS: Random, stratified, cluster sampling of the inhabitants > or =40 years of age from villages in the Meiktila District was performed; 2481 eligible participants were identified and 2076 participated in the study. METHODS: Visual acuity was measured using an E Snellen chart at 6 meters. Lid, ocular surface, and anterior segment examinations were performed at the slit lamp. MAIN OUTCOME MEASURES: Trachoma was graded as trachomatous trichiasis (TT) or CO according to the World Health Organization grading system. RESULTS: The population prevalence of trachoma (TT and CO) was 2.6% (95% confidence interval [CI]. 1.67%-3.42%). For every 1-year increase in age, the odds of trachoma increased by 5.3% (95% CI, 4.9%-5.7%). There was no significant effect of gender on the prevalence of trachoma (P = 0.5). No formal schooling was a strong predictor of trachoma (odds ratio, [OR], 4.9; 95% CI, 3.9-6.1), and having <3 children in the house was protective (OR, 0.75; 95% CI, 0.61-0.93); however, neither occupation nor the number of people in a household had an effect on trachoma. CONCLUSIONS: The prevalence of blinding trachoma in central Myanmar remains relatively low. This is a tribute to the success of the Burma Trachoma Control Program and demonstrates the need for such a program to remain an integral part of public health care and community health services to further diminish the prevalence of this condition. This will be facilitated by a focus on trachoma risk factors and further research into the prevalence of inflammatory trachoma within the pediatric population.