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1.  Fluorescein angiography vs. optical coherence tomography for diagnosis of uveitic macular edema 
Ophthalmology  2013;120(9):1852-1859.
To evaluate agreement between fluorescein angiography (FA) and optical coherence tomography (OCT) for diagnosis of macular edema in patients with uveitis.
Multicenter cross-sectional study
Four hundred seventy-nine eyes with uveitis of 255 patients
The macular status of dilated eyes with intermediate, posterior or panuveitis was assessed via Stratus-3 OCT and FA. Kappa statistics evaluated agreement between the diagnostic approaches.
Main Outcome Measures
Macular thickening (center point thickness ≥240 μm per reading center grading of OCT images-“MT”) and macular leakage (central subfield fluorescein leakage ≥0.44 disk areas per reading center grading of FA images-“ML”); agreement amongst these outcomes in diagnosing “macular edema.”
OCT (90.4%) more frequently returned usable information regarding macular edema than FA (77%) and biomicroscopy (76%). Agreement in diagnosis of MT and ML (κ=0.44) was moderate. ML was present in 40% of cases free of MT, whereas MT was present in 34% of cases without ML. Biomicroscopic evaluation for macular edema failed to detect 40% and 45% of cases of MT and ML respectively and diagnosed 17% and 17% of cases with macular edema which did not have MT or ML respectively; these results may underestimate biomicroscopic errors (ophthalmologists were not explicitly masked to OCT and FA results). Among eyes free of ML, phakic eyes without cataract rarely (4%) had MT. No factors were found that effectively ruled out ML when MT was absent.
OCT and FA offered only moderate agreement regarding macular edema status in uveitis cases, probably because what they measure (MT and ML) are related but non-identical macular pathologies. Given its lower cost, greater safety, and greater likelihood of obtaining usable information, OCT may be the best initial test for evaluation of suspected macular edema. However, given that ML cannot be ruled out if MT is absent and vice versa, obtaining the second test after a negative result on the first seems justified when detection of ML or MT would alter management. Given that biomicroscopic evaluation for macular edema frequently erred, ancillary testing for macular edema seems indicated when knowledge of ML or MT status would affect management.
PMCID: PMC3758459  PMID: 23706700
2.  Quantitative assessment of macular thickness in normal subjects and patients with diabetic retinopathy by scanning retinal thickness analyser 
AIMS—To evaluate the scanning retinal thickness analyser (RTA), a novel non-invasive imaging instrument, in diagnosing and quantitatively characterising diabetic macular oedema, and to investigate the relation between central macula thickness measured by RTA and other clinical examinations.
METHODS—Central macular thickness was measured using the RTA in 40 normal subjects and 60 patients with diabetic retinopathy. The reproducibility of the retinal thickness measurements was evaluated by calculating the mean of the inter- and intrasession variations. Central macular thickness was correlated with the results of visual acuity measurements, biomicroscopy, and fluorescein angiography.
RESULTS—Intra- and intersession reproducibility of the RTA in normal subjects was plus or minus 5.2% (16 µm) and plus or minus 6.1% (19 µm), respectively. The mean central macular thickness was 182 (SD 16) µm in normal subjects, 283 (116) µm in diabetic eyes without clinically significant macular oedema (CSMO), and 564 (168) µm in diabetic eyes with CSMO. Central macular thickness was significantly greater (p<0.001) in eyes with diabetic retinopathy than in normal subjects, even when macular thickening did not meet the standard for CSMO (p=0.019) measured by biomicroscopy. Although greater fluorescein leakage at the macula results in greater central macular thickness, only eyes with diffuse leakage had statistically significant macular thickening compared with normal subjects (p=0.022). Central macular thickness measured with the RTA was significantly correlated with the logarithmic converted visual acuity (r2= 0.76) in diabetic eyes.
CONCLUSION—Scanning RTA, which has good reproducibility, might be useful to quantitatively detect and monitor macular thickening in diabetic retinopathy. Central macular thickness was highly correlated with logarithmic converted visual acuity in diabetic macular oedema.

 Keywords: scanning retinal thickness analyser; macular thickness; diabetic retinopathy; macular oedema
PMCID: PMC1722802  PMID: 10209436
3.  Visual quality of life after macular hole surgery: outcome and predictive factors 
In the present study we evaluated the functional success after macular hole surgery in correlation to visual quality of life and looked for predictive factors determining surgical success.
Fifty‐nine patients that underwent pars plana vitrectomy for idiopathic macular hole were included. Follow‐up visits were performed in regular intervals after surgery and included a clinical examination, optical coherence tomography (OCT) and measurement of visual acuity. To assess the visual quality of life patients filled out the National Eye Institute 25‐item Visual Function Questionnaire (VFQ‐25) before and three months and one year after surgery.
Macular hole closure was achieved in 57 of 59 patients (97%). Mean visual acuity increased from 20/100 preoperatively to 20/34 one year after surgery (p = 0.02). Despite good visual acuity (20/27) in the fellow eye, visual quality of life (VFQ composite score) rose from 75.9 ± 14.4 (SD) to 81.5 ± 14.2 one year after surgery (p<0.001). Although there was no correlation between the increase in visual quality of life and visual acuity, the increase in VFQ‐25 could be well predicted: low visual acuity and significant impairment on VFQ‐25 testing preoperatively made patients most likely to benefit from macular hole surgery. A relatively high retinal thickness measurement at the hole border measured on OCT further increases the predictive value.
Macular hole surgery is associated with an increase in visual quality of life despite good visual acuity of the fellow eye. Preoperative visual acuity, VFQ‐25 value and partly OCT may help to predict the increase in patients' vision related quality of life after surgery.
PMCID: PMC1994732  PMID: 17077117
4.  Subconjunctival sirolimus in the treatment of diabetic macular edema 
Diabetic macular edema (DME) is a leading cause of blindness in the developed world. Sirolimus has been shown to inhibit the production, signaling, and activity of many growth factors relevant to the development of diabetic retinopathy. This phase I/II study assesses the safety of multiple subconjunctival sirolimus injections for the treatment of DME, with some limited efficacy data.
In this phase I/II prospective, open-label pilot study, five adult participants with diabetic macular edema involving the center of the fovea and best-corrected ETDRS visual acuity score of ≤74 letters (20/32 or worse) received 20 μl (440 μg) of subconjunctival sirolimus at baseline, month 2 and every 2 months thereafter, unless there was resolution of either retinal thickening on OCT or leakage on fluorescein angiography. Main outcome measures included best-corrected visual acuity and central retinal thickness on OCT at 6 months and 1 year, as well as safety outcomes.
Repeated subconjunctival sirolimus injections were well-tolerated, with no significant drug-related adverse events. There was no consistent treatment effect related to sirolimus; one participant experienced a 2-line improvement in visual acuity and 2 log unit decrease in retinal thickness at 6 months and 1 year, two remained essentially stable, one had stable visual acuity but improvement of central retinal thickness of 1 and 3 log units at 6 months and 1 year respectively, and one had a 2-line worsening of visual acuity and a 1 log unit increase in retinal thickness at 6 months and 1 year. Results in the fellow eyes with diabetic macular edema, not treated with sirolimus, were similar.
Subconjunctival sirolimus appears safe to use in patients with DME. Assessment of possible treatment benefit will require a randomized trial.
PMCID: PMC3183290  PMID: 21567211
Sirolimus; Diabetic retinopathy; Macular edema; mTOR
5.  Macular thickness changes evaluated with spectral domain optical coherence tomography after uncomplicated phacoemulsification 
Eye  2013;27(5):605-611.
To determine macular thickness changes after uncomplicated cataract surgery using spectral domain optical coherence tomography (OCT).
This was a prospective non-randomized, clinical study. Data were analysed for 40 healthy patients undergoing uneventful phacoemulsification. OCT measurements were performed before surgery and postoperatively at day 1, week 1 and 2, and month 1, 2, 3, and 6. The retinal map was divided into central point thickness (CPT), central 1-mm subfield (CSF), and two peripheral ring areas with diameters of 3 and 6 mm. Fellow eyes were used as controls. Retinal thickness change between the operated and fellow eyes were compared using unpaired t-test. Correlations were analysed using the Spearman or the Pearson analysis.
There was a progressive significant increase in retinal thickness of the operated eyes compared with the fellow eyes, with a peak at 1 month (P<0.0001) for the 3- and 6-mm areas and a peak at 2 months for CPT and CSF (P=0.01 and P<0.0001, respectively). At 6 months, retinal thickness was still significantly increased only in the peripheral areas (P<0.0001). There was no significant correlation between macular thickness changes and preoperative factors (age, axial length, anterior chamber depth, posterior vitreous detachment, best-corrected visual acuity), intraoperative factors (length of surgery, effective phaco time, phaco energy) or BCVA change.
The present study demonstrated a significant increase in macular thickness up to 6 months after uncomplicated cataract surgery. The most important finding was the regional pattern of retinal thickening with an early involvement of the parafoveal area.
PMCID: PMC3650275  PMID: 23449512
macular thickness; phacoemulsification; spectral domain optical coherence tomography; cystoid macular oedema
6.  A comparison between amblyopic and fellow eyes in unilateral amblyopia using spectral-domain optical coherence tomography 
To compare the macular retinal thickness and characteristics of optic nerve head (ONH) parameters in amblyopic and fellow eyes in patients with unilateral amblyopia.
Patients and methods
A total of 21 patients with unilateral amblyopia (14 patients with anisometropic amblyopia, four patients with strabismic amblyopia, and three patients with both) were examined using spectral-domain optical coherence tomography. The mean age of the patients was 8.5±3.5 years. The examined parameters included the mean macular (full, inner, and outer), ganglion cell complex and circumpapillary retinal nerve fiber layer (cpRNFL) thicknesses, and ONH parameters (rim volume, nerve head volume, cup volume, rim area, optic disc area, cup area, and cup-to-disc area ratio).
The amblyopic eyes were significantly more hyperopic than the fellow eyes (P<0.001). Among the macular retinal thickness parameters, the cpRNFL thickness (P<0.01), macular full retinal thickness (3 mm region) (P<0.01), and macular outer retinal thickness (1 and 3 mm regions) (P<0.05) were significantly thicker in the amblyopic eyes than in the fellow eyes, while the ganglion cell complex thickness, macular full retinal thickness (1 mm region), and macular inner retinal thickness (1 and 3 mm regions) were not significantly different. Among the ONH parameters, the rim area was significantly larger and the cup-to-disc area ratio was smaller in the amblyopic eyes than in the fellow eyes (P<0.05). None of the other ONH parameters were significantly different between the investigated eyes. The differences in the cpRNFL thickness and macular outer retinal thickness in the 1 mm region were significantly correlated with the difference in axial length (P<0.05, r=−0.48; P<0.01, r=−0.59, respectively) and refractive error (P<0.05, r=0.50; P<0.01, r=0.60, respectively). The other parameters were not significantly related to the difference in axial length, refractive error, or best corrected visual acuity.
We found significant differences in some of the morphological measurements between amblyopic and fellow eyes that appear to be independent of abnormalities in the visual cortex.
PMCID: PMC4230232  PMID: 25404852
anisometropic amblyopia; strabismic amblyopia; ganglion cell complex thickness; macular retinal thickness; peripapillary retinal nerve fiber layer thickness
7.  Short-term results of intravitreal dexamethasone implant (OZURDEX®) in treatment of recalcitrant diabetic macular edema: A case series 
Oman Journal of Ophthalmology  2012;5(2):79-82.
Dexamethasone Posterior-Segment Drug Delivery System is a novel, biodegradable, sustained-release drug delivery system (OZURDEX®) for treatment of macular edema following retinal vein occlusion and posterior uveitis. However, its potential role in management of diabetic macular edema has not been reported yet.
The aim was to evaluate the safety and efficacy of (OZURDEX®) in patients with recalcitrant diabetic macular edema (DME).
Setting and Design:
A retrospective, interventional case series from a tertiary eye care center in India is presented. Inclusion criteria comprised patients presenting with recalcitrant DME, 3 or more months after one or more treatments of macular laser photocoagulation and/or intravitreal anti-vascular endothelial growth factor (VEGF) injections. Exclusion criteria included history of corticosteroid-responsive intraocular pressure (IOP) rise, cataract extraction, or other intraocular surgery within 3 months. The main outcome measure was visual acuity at 1 and 4 months after OZURDEX® injection. Secondary outcome measures included change in central macular thickness on Optical coherence tomography (OCT) and changes in IOP following intravitreal OZURDEX® implant. Of 18 eyes (17 patients) with recalcitrant diabetic macular edema that underwent OZURDEX® implant, three eyes (two patients) had follow-up of more than 3 months post-injection.
Mean age of patients was 56 years. Mean duration of diabetes mellitus was 16.6 years. Systemic control of DM was good as assessed by FBS/PPBS and HbA1c. The pre-operative mean central macular thickness was 744.3 μm and improved to 144 and 570 μm at months 1 and 4, respectively. Preoperative mean BCVA was 0.6 logMAR units and improved to 0.3 and 0.46 logMAR units at month 1 and 4, respectively. The mean follow-up was 4.3 months (range 4-5 months).
OZURDEX® appears efficacious in management of recalcitrant diabetic macular edema. The results of the ongoing POSURDEX® study will elaborate these effects better.
PMCID: PMC3441033  PMID: 22993460
Dexamethasone; diabetes mellitus; diabetic macular edema; intravitreal implant; OZURDEX®
8.  Transconjunctival 25-gauge pars plana vitrectomy and internal limiting membrane peeling for chronic macular edema 
The purpose of this study was to investigate the visual and anatomic outcomes in patients with chronic macular edema who underwent 25-gauge pars plana vitrectomy with internal limiting membrane peeling.
This study was a retrospective chart review of 24 eyes from 21 patients who underwent 25-gauge pars plana vitrectomy and indocyanine green-assisted internal limiting membrane peeling for chronic macular edema. Preoperative and postoperative spectral-domain optical coherence tomography (OCT) was examined for macular thickness and macular volume. Outcomes and variables were analyzed using the two-tailed t-test and Spearman’s rank correlation coefficient.
Twenty-four eyes from 11 men and 10 women of mean age 69 (range 55–84) years were included. Four patients (17%) had chronic macular edema from uveitis, four (17%) from retinal vein occlusion, and 16 (67%) from diabetes. Mean visual acuity was 20/103 preoperatively and 20/87 postoperatively (P = 0.55). Sixty-three percent of the eyes had improved vision (47% better than 20/40), 21% maintained the same vision, and 17% had worse vision. Forty-seven percent of improved eyes and 30% of total eyes gained more than two lines of visual acuity (range −9 to +7 lines). Mean macular thickness was 455 μm preoperatively and 396 μm postoperatively (P = 0.29). Mean macular volume was 7.9 mm3 preoperatively and 7.5 mm3 postoperatively (P = 0.51). The strongest predictor of postoperative visual acuity was initial visual acuity (r = 0.673, P = 0.0003).
Even though a majority of patients had improved vision and decreased macular thickening after 25-gauge pars plana vitrectomy with internal limiting membrane peeling for chronic macular edema of various etiologies, the difference in visual acuity or macular thickening did not reach statistical significance.
PMCID: PMC3402127  PMID: 22848140
chronic macular edema; diabetes mellitus; internal limiting membrane peeling; 25-gauge vitrectomy; uveitis; vein occlusion
9.  Vitreo-retinal interface changes on optical coherence tomography in the fellow eyes of patients with macular hole 
To study the vitreo-retinal interface and macular changes on optical coherence tomography (OCT) in the fellow eyes of patients with macular hole.
Patients with idiopathic macular hole in one or both eyes presented to our institute between January 2003 and December 2009 were evaluated retrospectively. Demographic details, best-corrected visual acuity and vitreo-retinal interface, and macular changes of the fellow eye on OCT were studied.
Seventy patients underwent OCT of both eyes during the study period. The average age group was 61.96 years and 35 (50%) were females. Among the fellow eyes, normal foveal contour was noted in 36 (51.4%) eyes and 34 (48.6%) eyes were observed to have vitreo-retinal interface changes. Of them, 13 (18.6%) eyes had some stage of full thickness macular hole and 21 (30.0%) eyes had interface changes. There was no statistical correlation between involved eye lesions (P=0.64) or visual acuity (P=0.55) as predictors of development of either fellow eye lesions or poor visual acuity.
There is a significant chance of having vitreo-retinal interface findings in the fellow eyes of patients presenting with macular hole. OCT should be considered in both eyes of patients with macular hole to detect early changes in the fellow eyes, which may require an early intervention.
PMCID: PMC3755316  PMID: 23991391
macular hole; fellow eye; optical coherence tomography; vitreo-retinal interface
10.  Treatment of Adult-Onset Acute Macular Retinoschisis in Enhanced-S Cone Syndrome with Oral Acetazolamide 
American journal of ophthalmology  2008;147(2):307-312.e2.
To report on the efficacy of the oral carbonic anhydrase inhibitor (CAI), acetazolamide, in treating macular retinoschisis (RS) in the rare vitreoretinal dystrophy best known as the enhanced S-cone syndrome (ESCS).
Interventional case report.
Setting: University-based practice. Patient: A 48-year old Jewish Italian male with clinically, functionally and molecularly confirmed ESCS, due to homozygosity for the R311Q mutation in the NR2E3 gene, presented with sudden visual acuity loss (20/200) and metamorphopsia in the left eye resulting from acute, late-onset, asymmetric macular RS. Intervention: Open-label, off-label treatment with the oral CAI acetazolamide. Main Outcome Measure(s): Best corrected visual acuity, retinal thickness and retinal microanatomy, assessed by Stratus optical coherence tomography (OCT) criteria.
Following treatment, instituted one month after the acute-onset visual acuity loss, retinal thickness and microanatomic profile normalized in the affected eye, with restoration of 20/20 corrected visual acuity. The fellow eye, which had remained asymptomatic at 20/16 vision, had experienced mild paracentral macular RS evident by OCT criteria, which also resolved completely following oral CAI treatment. The outcome was maintained throughout the follow up period at a low maintenance dose.
Taken together with other recent reported benefits of topical and oral CAIs in the treatment of macular RS in X-linked retinoschisis, this interventional case report shows that CAIs can be used to treat effectively macular RS in general, and also specifically in ESCS.
PMCID: PMC2677970  PMID: 18835469
11.  Incidence of Choroidal Neovascularization in the Fellow Eye in the Comparison of Age-related Macular Degeneration Treatments Trials 
Ophthalmology  2013;120(10):2035-2041.
To assess the influence of drug, dosing regimen, and traditional, non-traditional, and genetic risk factors on the incidence of choroidal neovascularization (CNV) in the fellow eye of patients treated for CNV with ranibizumab or bevacizumab.
Cohort study of patients enrolled in a multicenter randomized clinical trial.
Patients with no CNV in the fellow eye at the time of enrollment in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT).
Eligibility criteria for the clinical trial required that study eyes have evidence on fluorescein angiography and optical coherence tomography (OCT) of CNV secondary to age-related macular degeneration (AMD) and visual acuity between 20/25 and 20/320. Treatment for the study eye was assigned randomly to either ranibizumab or bevacizumab and to three different regimens for dosing over a two-year period. The genotypes for four single nucleotide polymorphisms (SNPS) associated with risk of AMD were determined. Only patients without CNV in the fellow eye at baseline were considered at risk. CATT ophthalmologists examined patients every four weeks through two years and recorded treatment for CNV in the fellow eye.
Main Outcome Measures
Development of CNV in the fellow eye.
Among 1185 CATT participants, 727 (61%) had no CNV in the fellow eye at enrollment. At two years, CNV had developed in 75 (20.6%) of 365 patients treated with ranibizumab and 60 (16.6%) of 362 patients treated with bevacizumab (absolute difference 4.0%, 95% confidence interval (−1.7%, 9.6%); p=0.17). The risk ratio for pro re nata (PRN) dosing relative to monthly dosing was 1.1 (95% confidence interval (0.8, 1.6)). Greater elevation of the retinal pigment epithelium and fluid in the foveal center of the study eye were associated with increased incidence of CNV in the fellow eye. Incidence was not associated with genotype on rs1061170 (CFH), rs10490924 (ARMS2), rs11200638 (HTRA1), and rs2230199 (C3) (p > 0.35).
Through two years, there was no statistically significant difference between ranibizumab and bevacizumab in incidence of CNV in the fellow eye. Genotype on four SNPs previously found to be associated with AMD did not affect the risk of CNV in the fellow eye among CATT patients.
PMCID: PMC3758381  PMID: 23706946
12.  Macular retinal and choroidal thickness in unilateral relentless placoid chorioretinitis analyzed by swept-source optical coherence tomography 
The purpose of this study is to evaluate the retinal and choroidal thickness of the macular region in patients with unilateral relentless placoid chorioretinitis (RPC) and macular involvement. Patients diagnosed with RPC affecting only one eye underwent a comprehensive ophthalmologic examination including best-corrected visual acuity (BCVA), axial length (AL) measurement, slit-lamp examination, and color fundus and autofluorescence photography. The macular region was scanned by swept-source optical coherence tomography in the 1,050-nm wavelength. Automated segmentations of the retina and the choroid were used to obtain the corresponding thickness values.
A total number of three patients (two men and one woman; age range 17 to 62 years) were included. Eyes with clinically evident RPC had a mean AL of 24.62 ± 0.11 mm, whereas in the clinically healthy fellow eyes, the mean AL was 24.65 ± 0.03 (p = 0.70). The mean BCVA was 0.93 ± 0.16 in eyes with RPC, and 1.0 in all the fellow eyes (p = 0.70). Slit-lamp examination did not reveal any sign of vitreous inflammation in any cases. The mean macular retinal thickness was 288.10 ± 10.22 μm in eyes with RPC, and 300.30 ± 7.17 μm in the healthy fellow eyes (p = 0.20). The mean central choroidal thickness was 260.70 ± 140.60 μm in eyes with RPC, and 262.30 ± 123.10 μm in the fellow eyes (p = 0.99). The mean macular choroidal thickness was 248.60 ± 128.40 and 255.10 ± 123.60 μm, respectively (p = 0.99).
The pathogenesis of RPC remains unknown. No changes in the retinal and choroidal thickness were observed in the macular area of eyes diagnosed with RPC with macular involvement compared with the asymptomatic healthy fellow eyes. Further prospective studies are warranted in order to investigate the role of the choroid in cases of RPC.
PMCID: PMC4182277  PMID: 25279015
Choroidal thickness; Uveitis; Relentless placoid chorioretinitis; Swept-source OCT
13.  A Proposed Method of Logarithmic Transformation of Optical Coherence Tomography Data for use in Clinical Research 
Ophthalmology  2010;117(8):1512-1516.
To evaluate a logarithmic transformation of retinal thickness measurements from optical coherence tomography as a new approach to assess clinically meaningful changes in retinal thickness.
Methodological evidence based review.
There were no participants.
Standard published approaches for assessing change in retinal thickness over time, as measured by optical coherence tomography (OCT), were compared with a new approach based on a logarithmic transformation of the retinal thickness data. Comparative examples were derived using published data from a clinical trial comparing intravitreal corticosteroid injections for diabetic macular edema with standard laser treatment.
Main Outcome Measures
Comparative examples using Diabetic Retinopathy Clinical Research Network data.
Logarithmic transformation of retinal thickness data results in a more normalized distribution of OCT data and allows for data analyses assessing proportionate changes in retinal thickness during followup.
For analysis of grouped data, a logarithmic transformation of the OCT retinal thickness measurements (logOCT) provides several analytic advantages. Distributions of retinal thickness in groups of eyes with diabetic macular edema, and many other causes of macular thickening, tend to be skewed to the right, and the logOCT transformation tends to normalize these distributions, which has value for statistical comparisons. For assessing whether the observed OCT change in a patient is real (and not due to testing variability), a one step log scale change exceeds the measurement error for all degrees of retinal thickness in current instruments. In addition, this log scale is similar to the logarithm of the minimum angle of resolution (logMAR) scale used for visual acuity. Steps on the log scale for change in thickness seem better related to clinical importance than the actual change in microns because each step on the log scale is the same proportionate change in thickness, with a three step change equaling a halving or doubling of thickness, regardless of the baseline value. Transformation of OCT retinal thickness data to logOCT may assist in the assessment of clinically meaningful changes in retinal thickness just as use of the logMAR scale has helped assess clinically meaningful changes in visual acuity.
PMCID: PMC2916055  PMID: 20363505
14.  Baseline Predictors of Visual Acuity and Retinal Thickness Outcomes in Patients with Retinal Vein Occlusion. SCORE Study Report 10 
Ophthalmology  2011;118(2):345-352.
To investigate baseline factors significantly associated with visual acuity and central retinal thickness outcomes in patients with macular edema secondary to retinal vein occlusion in the Standard Care versus COrticosteroid for REtinal Vein Occlusion (SCORE) Study.
Two multicenter, randomized clinical trials: one evaluating participants with central retinal vein occlusion (CRVO) and the other evaluating participants with branch retinal vein occlusion (BRVO).
Participants with ≥1 year follow-up data, including 238 with CRVO and 367 with BRVO.
Visual acuity was measured by the electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS) method and central retinal thickness by optical coherence tomography (OCT). Logistic and ordinary least squares regression related these outcomes to 20 baseline measures. Multiple p-values were adjusted to control the false discovery rate.
Main Outcome Measures
Outcome measures of visual acuity letter score included absolute change from baseline, a gain of ≥15 from baseline, and a loss of ≥15 from baseline. Outcome measures of center point thickness included absolute change from baseline, a measurement of ≤250 microns, and a measurement of ≥500 microns. Outcomes were assessed at 1 and 2 years.
For CRVO and BRVO, younger age was significantly associated with improved visual acuity and central retinal thickness outcomes. For CRVO, treatment with triamcinolone and less severe anatomical abnormalities of the retina (center point thickness and areas of retinal hemorrhage, thickening, and fluorescein leakage) were predictive of better visual acuity outcomes. For BRVO, lack of a history of coronary artery disease was predictive of improved visual acuity outcomes. For center point thickness outcomes based on OCT, shorter duration of macular edema was significantly associated with improvement in both disease entities. For CRVO, higher baseline visual acuity letter score, and for BRVO, lower baseline visual acuity letter score, presence of dense macular hemorrhage and no prior grid photocoagulation were predictive of favorable OCT outcomes.
Several factors were predictive of better visual acuity outcomes, including younger age, and predictive of more favorable OCT outcomes, including shorter duration of macular edema. These baseline factors may assist clinicians in predicting the course of disease for patients with CRVO and BRVO.
PMCID: PMC3020981  PMID: 20926135
15.  Diabetic retinopathy (treatment) 
Clinical Evidence  2011;2011:0702.
Diabetic retinopathy is the most common cause of blindness in the UK, with older people and those with worse diabetes control, hypertension, and hyperlipidaemia being most at risk. Diabetic retinopathy can cause microaneurysms, haemorrhages, exudates, changes to blood vessels, and retinal thickening.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments in people with diabetic retinopathy? What are the effects of treatments for vitreous haemorrhage? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
We found 58 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
In this systematic review we present information relating to the effectiveness and safety of the following interventions: peripheral retinal laser photocoagulation, focal and grid laser photocoagulation for maculopathy, corticosteroids for macular oedema, vascular endothelial growth factor inhibitors, and vitrectomy for vitreous haemorrhage.
Key Points
Diabetic retinopathy is the most common cause of blindness in the UK, with older people and those with worse diabetes control, hypertension, and hyperlipidaemia most at risk. Diabetic retinopathy can cause microaneurysms, haemorrhages, exudates, changes to blood vessels, and retinal thickening.
Peripheral retinal laser photocoagulation reduces the risk of severe visual loss compared with no treatment in people with preproliferative (moderate/severe non-proliferative) retinopathy and maculopathy. We don't know if any one type of laser treatment is superior to another.We don't know whether peripheral laser photocoagulation is effective in people with background or preproliferative (non-proliferative) retinopathy without maculopathy because we found no RCTs assessing it in this population.
The benefits of laser photocoagulation are more notable in people with proliferative retinopathy than in those with maculopathy. Focal macular laser photocoagulation reduces the risk of moderate visual loss in eyes with clinically significant macular oedema plus mild to moderate preproliferative (moderate/severe non-proliferative) diabetic retinopathy, compared with no treatment. Grid photocoagulation to zones of retinal thickening may improve visual acuity in eyes with diffuse maculopathy. Photocoagulation is unlikely to be beneficial in eyes with maculopathy but without clinically significant macular oedema.
Intravitreal triamcinolone acetonide improves visual acuity and reduces macular thickness in eyes with macular oedema refractory to previous macular laser photocoagulation, but repeated injections are needed to maintain benefit. Secondary ocular hypertension and progression of cataract are common complications with intravitreal triamcinolone; infectious endophthalmitis is rare.
Intravitreal vascular endothelial growth factor (VEGF) inhibitors pegaptanib and bevacizumab improve visual acuity and reduce macular thickness in eyes with centre-involving diabetic macular oedema and vision loss, but repeat intravitreal injections are needed to maintain benefit. Bevacizumab is not licensed for intraocular use.We don't know the long-term ocular and systemic safety of bevacizumab.We don't know if any one intravitreal VEGF inhibitor or treatment regimen is superior to another.We don't know whether combination treatment with VEGF inhibitor injection plus macular laser photocoagulation is effective as we found only one trial assessing ranibizumab as part of combined treatment.
Vitrectomy can reduce visual loss if performed early in people with vitreous haemorrhage, especially if they have severe proliferative retinopathy. We don't know whether vitrectomy is effective in people with vitreous haemorrhage plus maculopathy as we found no RCTs assessing it.
PMCID: PMC3217806  PMID: 21609511
16.  Relationship between Photoreceptor Outer Segment Length and Visual Acuity in Diabetic Macular Edema 
Retina (Philadelphia, Pa.)  2010;30(1):63-70.
To quantify photoreceptor outer segment (PROS) length in patients with diabetic macular edema (DME) using spectral domain optical coherence tomography (OCT), and to describe the correlation between PROS length and visual acuity in this group of patients.
Prospective study.
Twenty-seven consecutive patients (30 eyes) with DME.
Three SD-OCT scans were performed on all eyes during each session using Cirrus™ HD-OCT. A prototype algorithm was developed for quantitative assessment of PROS length. Retinal thicknesses and PROS lengths were calculated for three parameters; macular grid (6mm × 6mm), central subfield (1mm), and center foveal point (0.33mm). Intrasession repeatability was assessed using coefficient of variation (CVW) and intraclass correlation coefficient (ICC). Association between retinal thickness and PROS length with visual acuity was assessed using linear regression and Pearson correlation analyses.
Main Outcome Measure
Intrasession repeatability of macular parameters, and correlation of these parameters with visual acuity.
Mean retinal thickness and PROS length were 298-381 μm and 30-32 μm, respectively, for macular parameters assessed in this study. CVW values were 0.75-4.13% for retinal thickness, and 1.97-14.01% for PROS length. ICC values were 0.96-0.99 and 0.73-0.98 for retinal thickness and PROS length, respectively. Slopes from linear regression analyses assessing the association of retinal thickness and visual acuity were not significantly different from zero (p>0.20), whereas the slopes of PROS length and visual acuity were significantly different from zero (p<0.0005). Correlation coefficients for macular thickness and visual acuity ranged from 0.13 to 0.22, while coefficients for PROS length and visual acuity ranged from -0.61 to -0.81.
PROS length can be quantitatively assessed using Cirrus™ HD-OCT. Although the intrasession repeatability of PROS measurements was less than that of macular thickness measurements, the stronger correlation of PROS length with visual acuity suggests that PROS measures may be more directly related to visual function. PROS length may be a useful physiologic outcome measure, both clinically and as a direct assessment of treatment effects.
PMCID: PMC3021331  PMID: 19952996
17.  In vivo identification of morphologic retinal abnormalities in neuromyelitis optica 
Neurology  2013;80(15):1406-1414.
To assess eyes with neuromyelitis optica (NMO) for morphologic retinal abnormalities utilizing high-definition optical coherence tomography (OCT) imaging.
In this cross-sectional study, 39 patients with NMO spectrum disorders and 39 age- and sex-matched healthy controls underwent spectral-domain OCT and visual function testing.
Microcystic macular edema (MME) of the inner nuclear layer (INL) was identified in 10 of 39 patients (26%) and was exclusively found in eyes with a history of optic neuritis (ON). MME eyes had lower high- and low-contrast letter-acuity scores (100%: p = 0.002; 2.5%: p = 0.002; 1.25%: p = 0.004), lower peripapillary retinal nerve fiber layer (RNFL) thickness (p = 0.04), lower macular RNFL thickness (p = 0.004), lower ganglion cell layer + inner plexiform layer (GCIP) thickness (p = 0.007), higher INL thickness (p < 0.001), and a greater number of ON episodes (p = 0.008) relative to non-MME eyes with a history of ON. After adjusting for history of multiple ON episodes, these findings remained significant for macular-RNFL thickness (p = 0.03), INL thickness (p < 0.001), and 100% and 2.5% contrast letter-acuity scores (p = 0.008 and p = 0.03, respectively). NMO spectrum eyes without ON history had lower macular RNFL thickness (p = 0.003), GCIP thickness (p = 0.002), outer nuclear layer thickness (p = 0.02), and low-contrast letter-acuity scores (2.5%: p = 0.03; 1.25%: p = 0.002) compared to healthy controls.
We have identified a pattern of retinal morphologic abnormalities in NMO that is associated with severe retinal axonal and neuronal loss and corresponding visual disability. MME may contribute to poor visual outcomes following NMO-associated ON or alternatively represent a marker of ON severity. Additionally, our results support that subclinical involvement of the anterior visual pathway may occur in NMO spectrum disorders.
PMCID: PMC3662269  PMID: 23516321
18.  Spectral domain optical coherence tomography in patients after successful management of postoperative endophthalmitis following cataract surgery by pars plana vitrectomy 
BMC Ophthalmology  2014;14:76.
Acute severe postoperative endophthalmitis may lead to severe vision loss. The aim of this study was the analysis of macular microstructure imaged by spectral domain optical coherence tomography in patients after pars plana vitrectomy due to postcataract endophthalmitis.
A cross sectional study was carried out in 17 patients who had cataract surgery in both eyes and underwent unilateral pars plana vitrectomy due to postcataract endophthalmitis. Postoperative best corrected visual acuity was determined in both eyes. Evaluation of macular thickness, macular volume, peripapillary retinal nerve fiber layer thickness and choroidal thickness using enhanced depth imaging technique was performed by spectral domain optical coherence tomography. The measurements obtained in the operated eye were compared to the fellow eye by Wilcoxon matched pair test. Correlation test was performed by Spearman rank order.
A mean postoperative best corrected visual acuity of 63 ± 30 ETDRS letters versus 75 ± 21 letters was achieved in the study and fellow eyes, respectively, after a mean of 5.3 ± 4.5 months (p = 0.1). The mean macular thickness was 320.6 ± 28.8 μm SD in the study eyes compared to 318.4 ± 18.8 μm in the fellow eyes (p = 0.767). No differences were noted in macular volume (p = 0.97) and in peripapillary retinal nerve fiber layer thickness (p = 0.31). Choroidal thickness was significantly lower in the study eyes compared to the fellow eyes (p = 0.018). Epiretinal membrane was found in 7 eyes after endophthalmitis, while in the fellow eyes only in 3 cases (p = 0.13, Fisher’s exact test).
Choroidal thickness decreased significantly after endophthalmitis, but there was no functional correlation with the changes in choroidal microstructure. The development of epiretinal membranes may be associated with either vitrectomy or endophthalmitis in the history. Absence of other significant structural and morphological findings shows that successful treatment may guarantee good clinical results even in long term after this severe postoperative complication.
PMCID: PMC4077685  PMID: 24885759
Spectral domain optical coherence tomography; Postoperative endophthalmitis; Enhanced depth imaging; Choroidal thickness; Vitrectomy
19.  Comparison of bromfenac 0.09% QD to nepafenac 0.1% TID after cataract surgery: pilot evaluation of visual acuity, macular volume, and retinal thickness at a single site 
The purpose of this study was to investigate the clinical outcomes of bromfenac ophthalmic solution 0.09% once daily (QD) and nepafenac 0.1% ophthalmic suspension three times daily following cataract extraction with posterior chamber intraocular lens implantation, specifically looking at any differences in Early Treatment Diabetic Retinopathy Study visual acuities, macular volume, and/or retinal thickness changes.
Subjects were randomly assigned to receive either bromfenac (n = 10) QD or nepafenac (n = 10) three times daily. Dosing began 3 days before cataract surgery, continuing to day 21 postsurgery. In addition to the investigated nonsteroidal antiinflammatory drug regimen, all subjects received antiinfective intraoperative and postoperative standard of care. Subjects were followed at 1 day and 1, 3, and 6 weeks postoperatively. Study visit assessments included best-corrected visual acuity, biomicroscopy, summed ocular inflammation score (anterior chamber cells and flare grading), intraocular pressure measurement, adverse event recording, and concomitant medication review. Optical coherence tomography was performed at 1, 3, and 6 weeks.
Both treatment groups had similar baseline measurements. Outcomes for mean letters read (P = 0.318), mean change in macular volume (P = 0.665), and retinal thickness (P = 0.552) were not statistically different between the groups from baseline through week six, although independently only the bromfenac group demonstrated a statistically significant improvement in letters gained from baseline to week six (P = 0.040). In the same time period, mean macular volume and retinal thickening worsened in the nepafenac group, demonstrating a statistically significant increase (P = 0.006) at week six for macular volume when compared to baseline. One subject in the nepafenac group experienced recurrent inflammation at week six, was unmasked, and then rescued with bromfenac 0.09% QD and difluprednate 0.05% QD.
Both bromfenac and nepafenac resulted in positive clinical outcomes of Early Treatment Diabetic Retinopathy Study visual acuities. Postoperative measurements of macular volume and retinal thickness of bromfenac subjects showed a trend toward improved vision, less retinal thickening, and more stable macular volumes overall.
PMCID: PMC3399390  PMID: 22815642
NSAIDs; phacoemulsification; inflammation; cataract; macular volume; retinal thickness
20.  Regression of early diabetic macular oedema is associated with prevention of dark adaptation 
Eye  2011;25(12):1546-1554.
Dark-adapted rods consume oxygen at high rates and light adaptation decreases this oxygen burden and can have therapeutic effects on diabetic macular oedema (DMO).
Patients with mild non-proliferative diabetic retinopathy (DR) and early, untreated non-sight-threatening DMO slept for 6 months wearing masks that illuminated the eyelid of one closed eye by 505 nm light. Exclusion criteria were any concomitant eye disease, DR >ETDRS grade 35, and other systemic diseases. Primary outcome: change of OCT retinal thickness in the local region where oedema was present.
A total of 34 out of 40 patients completed the study. Mean baseline OCT macular cube thickness was equivalent for study and fellow eyes. But study eyes had a greater mean thickness in the central subfield zone 1 (282±53 μm) vs (256±19 μm) the fellow eyes. Twenty-eight study eyes showed intraretinal cysts compared with nine in the fellow eyes. At 6 months, only 19 study eyes had cysts while cysts were seen in 20 fellow eyes. After 6 months, the worst affected ETDRS zone and the central subfield zone 1 reduced in thickness in study eyes only by 12 μm (95% CI 20 to −7, P=0.01). The secondary outcomes of change in visual acuity, achromatic contrast sensitivity, and microperimetric thresholds improved significantly in study eyes and deteriorated in fellow eyes.
Sleeping in dim light that can keep rods light adapted may reverse the changes of DMO.
PMCID: PMC3234487  PMID: 22020171
lightmasks; diabetic macular oedema; hypoxia; dark; adaptation
21.  Stage 0 Macular Holes: Observations by Optical Coherence Tomography 
Ophthalmology  2004;111(11):2027-2032.
To introduce the concept of a stage 0 macular hole based on optical coherence tomographic observations of the vitreoretinal interface in fellow eyes of patients with unilateral idiopathic macular holes, and to evaluate the subsequent risk of progression to a full-thickness macular hole.
Retrospective observational case series.
Ninety-four patients with a unilateral stage 2, 3, or 4 full-thickness macular hole.
The medical records of patients with a unilateral macular hole diagnosed between 1994 and 2000 at the New England Eye Center were reviewed.
Main Outcome Measure
Development of a full-thickness macular hole in the fellow eye on biomicroscopic fundoscopy or optical coherence tomography (OCT).
In 27 (28.7%) of 94 clinically normal fellow eyes, OCT detected an abnormality of the vitreoretinal interface but normal foveal anatomy. The vitreoretinal abnormalities were further subclassified into severe (4 eyes), moderate (8 eyes), and mild (15 eyes) based on the intensity and morphology of the OCT signal. One of the 4 (25%) severe cases progressed to a full-thickness macular hole, 4 of the 8 (50%) moderate cases became full-thickness macular holes, and no (0%) mild cases progressed to a full-thickness macular hole. Severe and moderate eyes seemed to share characteristic features on OCT that increased their risk of macular hole development (stage 0 macular hole). The macular hole–free survival at 48 months was 94% for stage 0–negative patients, versus 54% for stage 0–positive patients. Univariate analysis revealed that the presence of a stage 0 macular hole was significantly associated with an almost 6-fold increase in the risk of macular hole formation (relative risk: 5.8, 95% confidence interval: 1.16–28.61, P = 0.03).
A stage 0 macular hole has a normal biomicroscopic appearance clinically, but has salient features on OCT as a result of oblique vitreous traction. Optical coherence tomographic findings consist of a normal foveal contour and normal retinal thickness and must include the presence of a preretinal, minimally reflective, thin band inserting obliquely on at least one side of the fovea. The presence of a stage 0 macular hole in the fellow eye is a significant risk factor for the development of a second macular hole.
PMCID: PMC1941774  PMID: 15522368
22.  Microcystic macular oedema in multiple sclerosis is associated with disease severity 
Brain  2012;135(6):1786-1793.
Macular oedema typically results from blood–retinal barrier disruption. It has recently been reported that patients with multiple sclerosis treated with FTY-720 (fingolimod) may exhibit macular oedema. Multiple sclerosis is not otherwise thought to be associated with macular oedema except in the context of comorbid clinical uveitis. Despite a lack of myelin, the retina is a site of inflammation and microglial activation in multiple sclerosis and demonstrates significant neuronal and axonal loss. We unexpectedly observed microcystic macular oedema using spectral domain optical coherence tomography in patients with multiple sclerosis who did not have another reason for macular oedema. We therefore evaluated spectral domain optical coherence tomography images in consecutive patients with multiple sclerosis for microcystic macular oedema and examined correlations between macular oedema and visual and ambulatory disability in a cross-sectional analysis. Participants were excluded if there was a comorbidity that could account for the presence of macular oedema, such as uveitis, diabetes or other retinal disease. A microcystic pattern of macular oedema was observed on optical coherence tomography in 15 of 318 (4.7%) patients with multiple sclerosis. No macular oedema was identified in 52 healthy controls assessed over the same period. The microcystic oedema predominantly involved the inner nuclear layer of the retina and tended to occur in small, discrete patches. Patients with multiple sclerosis with microcystic macular oedema had significantly worse disability [median Expanded Disability Score Scale 4 (interquartile range 3–6)] than patients without macular oedema [median Expanded Disability Score Scale 2 (interquartile range 1.5–3.5)], P = 0.0002. Patients with multiple sclerosis with microcystic macular oedema also had higher Multiple Sclerosis Severity Scores, a measure of disease progression, than those without oedema [median of 6.47 (interquartile range 4.96–7.98) versus 3.65 (interquartile range 1.92–5.87), P = 0.0009]. Microcystic macular oedema occurred more commonly in eyes with prior optic neuritis than eyes without prior optic neuritis (50 versus 27%) and was associated with lower visual acuity (median logMAR acuity of 0.17 versus −0.1) and a thinner retinal nerve fibre layer. The presence of microcystic macular oedema in multiple sclerosis suggests that there may be breakdown of the blood–retinal barrier and tight junction integrity in a part of the nervous system that lacks myelin. Microcystic macular oedema may also contribute to visual dysfunction beyond that explained by nerve fibre layer loss. Microcystic changes need to be assessed, and potentially adjusted for, in clinical trials that evaluate macular volume as a marker of retinal ganglion cell survival. These findings also have implications for clinical monitoring in patients with multiple sclerosis on sphingosine 1-phosphate receptor modulating agents.
PMCID: PMC3359753  PMID: 22539259
multiple sclerosis; optical coherence tomography; retina; macular oedema
23.  Optical Coherence Tomography for Age-Related Macular Degeneration and Diabetic Macular Edema 
Executive Summary
The purpose of this evidence-based review was to examine the effectiveness and cost-effectiveness of spectral-domain (SD) optical coherence tomography (OCT) in the diagnosis and monitoring of patients with retinal disease, specifically age-related macular degeneration (AMD) and diabetic macular edema (DME). Specifically, the research question addressed was:
What is the sensitivity and specificity of spectral domain OCT relative to the gold standard?
Clinical Need: Target Population and Condition
The incidence of blindness has been increasing worldwide. In Canada, vision loss in those 65 years of age and older is primarily due to AMD, while loss of vision in those 18 years of age and older is mainly due to DME. Both of these conditions are diseases of the retina, which is located at the back of the eye. At the center of the retina is the macula, a 5 mm region that is responsible for what we see in front of us, our ability to detect colour, and fine detail. Damage to the macula gives rise to vision loss, but early detection of asymptomatic disease may lead to the prevention or slowing of the vision loss process.
There are two main types of AMD, ‘dry’ and ‘wet’. Dry AMD is the more prevalent of the two, accounting for approximately 85% of cases and characterized by small deposits of extracellular material called “drusen” that build up in Bruch’s membrane of the eye. Central vision loss is gradual with blurring and eventual colour fading. Wet AMD is a less prevalent condition (15% of all AMD cases) but it accounts for 90% of severe cases. It’s characterized by the appearance of retinal fluid with vision loss due to abnormal blood vessels/leakage within weeks to months of diagnosis. In 2003, the Canadian National Institute for the Blind (CNIB) prevalence estimate for AMD was 1 million Canadians, including approximately 400,000 affected Ontarians. The incidence in 2003 was estimated to be 78,000 new cases in Canada, with approximately one-third of these cases arising in Ontario (n=26,000). Over the next 25 years, the number of new cases is expected to triple.
DME is caused by complications of diabetes mellitus, both Type 1 and Type 2. It is estimated that 1-in-4 persons with diabetes has this condition, though it occurs more frequently among those with type 2 diabetes. The condition is characterized by a swelling of the retina caused by leakage of blood vessels at the back of the eye. In early stages of the disease, vision may still be normal but it can degrade rapidly in later stages. In 2003, the CNIB prevalence estimate for DME was 0.5 million Canadians, with approximately 200,000 Ontarians affected. The incidence of DME is more difficult to ascertain; however, based on an annual incidence rate of 0.8% (for those 20 years of age or older) and the assumption that 1-in-4 persons with diabetes is affected, the incidence of DME in Ontario is estimated to be 21,000 new cases per year.
Optical Coherence Tomography
Prior to the availability of OCT, the standard of care in the diagnosis and/or monitoring of retinal disease was serial testing with fluorescein angiography (FA), biomicroscopy (BM), and stereo-fundus photography (SFP). Each of these is a qualitative measure of disease based on subjective evaluations that are largely dependent on physician expertise. OCT is the first quantitative visual test available for the diagnosis of eye disease. As such, it is allows for a more objective evaluation of the presence/absence of retinal disease and it is the only test that provides a measure of retinal thickness. The technology was developed at the Michigan Institute of Technology (MIT) in 1991 as a real-time imaging modality and is considered comparable to histology. It’s a light-wave based technology producing cross-sectional images with scan rates and resolution parameters that have greatly improved over the last 10 years. It’s also a non-invasive, non-contact visual test that requires just 3 to 5 minutes to assess both eyes.
There are two main types of OCT system, both licensed by Health Canada as class II devices. The original patent was based on a time domain (TD) system (available from 1995) that had an image rate of 100 to 400 scans per second and provided information for a limited view of the retina with a resolution in the range of 10 to 20 μm. The newer system, spectral domain (SD) OCT, has been available since 2006. Improvements with this system include (i) a faster scan speed of approximately 27,000 scans per second; (ii) the ability to scan larger areas of the retina by taking six scans radially-oriented 30 degrees from each other; (iii) increased resolution at 5μm; and (iv) ‘real-time registration,’ which was not previously available with TD.
The increased scan speed of SD systems enables the collection of additional real-time information on larger regions of the retina, thus, reducing the reliance on assumptions required for retinal thickness and volume estimates based on software algorithms. The faster scan speed also eliminates image distortion arising from patient movement (not previously possible with TD), while the improvement in resolution allows for clearer and more distinguishable retinal layers with the possibility of detecting earlier signs of disease. Real-time registration is a new feature of SD that enables the identification of specific anatomical locations on the retina, against which subsequent tests can be evaluated. This is of particular importance in the monitoring of patients. In the evaluation of treatment effects, for example, this enables the same anatomic retinal location to be identified at each visit.
Literature Search
A literature search was performed on February 13, 2009 using Ovid MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, the Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published from January 2003 to February 2009. The subject headings and keywords searched included AMD, DME, and OCT (the detailed search strategy can be viewed in Appendix 1). Excluded were case reports, comments, editorials, non-systematic reviews, and letters. Abstacts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria, full-text articles were obtained. In total, 542 articles were included for review.
English-language articles and health technology assessments.
RCTs and observational studies of OCT and AMD or DME.
Studies focusing on either diagnosis or monitoring of disease.
Studies in which outcomes were not specific to those of interest in this report.
Studies of pediatric populations.
Studies on OCT as a screening tool.
Studies that did not assess comparative effectiveness of OCT with a referent, as specified below in “Comparisons of Interest”.
Outcomes of Interest
Studies of sensitivity, specificity.
Comparisons of Interest
Evidence exists for the following comparisons of interest:
OCT compared with the reference “fluorescein angiography” for AMD.
OCT compared with the reference “biomicroscopy” or “stereo or fundus photography” for DME.
Summary of Existing Evidence
No evidence for the accuracy of SD OCT compared to either FA, BM or SFP was published between January 2006 to February 2009; however, two technology assessments were found, one from Alberta and the other from Germany, both of which contain evidence for TD OCT. Although these HTAs included eight studies each, only one study from each report was specific to this review. Additionally, one systematic review was identified for OCT and DME. It is these three articles, all pertaining to time and not spectral domain OCT, as well as comments from experts in the field of OCT and retinal disease, that comprise the evidence contained in this review.
Upon further assessment and consultations with experts in the methodology of clinical test evaluation, it was concluded that these comparators could not be used as references in the evaluation of OCT. The main conclusion was that, without a third test as an arbiter, it is not possible to directly compare the sensitivity and specificity of OCT relative to either FA for AMD and stereo- or fundus – photography for DME. Therefore, in the absence of published evidence, it was deemed appropriate to consult a panel of experts for their views and opinions on the validity of OCT and its utility in clinical settings. This panel consisted of four clinicians with expertise in AMD and/or DME and OCT, as well as a medical biophysicist with scientific expertise in ocular technologies. This is considered level 5 evidence, but in the absence of an appropriate comparator for further evaluation of OCT, this may be the highest level of evidence possible.
Summary of Findings
The conclusions for SD OCT based on Level 5 evidence, or expert consultation, are as follows:
OCT is considered an essential part of the diagnosis and follow-up of patients with DME and AMD.
OCT is adjunctive to FA for both AMD and DME but should decrease utilization of FA as a monitoring modality.
OCT will result in a decline in the use of BM in the monitoring of patients with DME, given its increased accuracy and consistency.
OCT is diffusing rapidly and the technology is changing. Since FA is still considered pivotal in the diagnosis and treatment of AMD and DME, and there is no common outcome against which to compare these technologies, it is unlikely that RCT evidence of efficacy for OCT will ever be forthcoming.
In addition to the accuracy of OCT in the detection of disease, assessment of the clinical utility of this technology included a rapid review of treatment effects for AMD and DME. The treatment of choice for AMD is Lucentis®, with or without Avastin® and photodynamic therapy. For DME the treatment of choice is laser photocoagulation, which may be replaced with Lucentis® injections (Expert consultation). The evidence, as presented in systematic reviews and other health technology assessments, indicates that there are effective treatments available for both AMD and DME.
Considerations for the Ontario Health System
OCT testing is presently an uninsured service in Ontario with patients paying approximately $150 out-of-pocket per test. Several provinces do provide funding for this procedure, including British Columbia, Alberta, Saskatchewan, Newfoundland, Nova Scotia, Prince Edward Island, and the Yukon Territory. Provinces that do not provide such funding are Quebec, Manitoba and New Brunswick.
The demand for OCT is expected to increase with aging of the population.
PMCID: PMC3377511  PMID: 23074517
24.  Differential Macular Morphology in Patients with RPE65-, CEP290-, GUCY2D-, and AIPL1-Related Leber Congenital Amaurosis 
This study evaluated possible correlations between the microanatomic macular structures, as measured by spectral-domain optical coherence tomography in Leber congenital amaurosis patients with mutations in RPE65, CEP290, GUCY2D, or AIPL1. Phenotypic variations of macular microstructures were observed among LCA patients with different genotypes.
To evaluate genotypic and macular morphologic correlations in patients with RPE65-, CEP290-, GUCY2D-, or AIPL1-related Leber congenital amaurosis (LCA) using spectral-domain optical coherence tomography (SD-OCT).
SD-OCT macular scans were performed in 21 patients, including 10 with RPE65, 7 with CEP290, 3 with GUCY2D, and 1 with AIPL1 mutations. An image processing software was used to manually draw segmentation lines by three observers. Lamellar structure was evaluated based on the number of retinal layers on segmented images. Total retinal thickness was measured at the central macular and perifoveal areas by using an automated algorithm.
All three patients with GUCY2D mutations (age range, 20–53 years) retained six retinal layers with visible photoreceptor inner/outer segment juncture (PSJ). However, the preservation of lamellar structures did not parallel better visual acuity. Patients with other mutations had poorly defined PSJ and disorganized retinal lamellar structures, where only one to three retinal layers could be observed. Patients with CEP290 mutations trended to have retention of the outer nuclear layer at the fovea and macular thickening, especially at younger ages. In patients with RPE65 (age range, 20–71 years) and AIPL1 mutations (age, 22 years), macular thickness was markedly decreased. Disorganization of retinal lamellar structures in the RPE65 group trended toward a worsening with increasing age.
Variations of macular microstructures were observed among LCA patients with different genotypes. Disorganization of retinal lamellar structure was generally age related. Preservation of retinal microanatomic structures may not be associated with better visual acuity.
PMCID: PMC2868490  PMID: 19959640
25.  Macular pigment levels following successful macular hole surgery 
The British Journal of Ophthalmology  2005;89(9):1105-1108.
Aim: Macular pigment (MP) is composed of two hydroxycarotenoids contained within the photoreceptors and the axons of the central neurosensory retina, with peak concentrations in the Henle layer. A full thickness macular hole (FTMH) is characterised by absence of all retinal layers in an area centred at the former centre of the fovea. The authors report the results of a study designed to investigate MP levels in patients following successful FTMH surgery, using Raman spectroscopy, and to correlate these findings with functional and topographic outcomes.
Methods: The following details were recorded for 12 eyes of 12 patients following successful closure of a FTMH: best corrected visual acuity; macula threshold test, fixation, fundus photography, and macular pigment levels using Raman spectroscopy. High resolution imaging of the retina using optical coherence tomography (OCT) was performed in nine of the 12 study eyes.
Results: Mean (SD) best corrected visual acuity was 0.6 (0.4) and improved significantly from preoperative levels. On macula threshold testing of the operated eye, a central scotoma was detectable in one eye only (8.3%). MP levels were demonstrable in 10 of the 12 study eyes following successful FTMH surgery. MP levels were higher in three study eyes, and lower in seven study eyes, when compared with the fellow eye. Of the three pairs of eyes where MP levels were greater in the study eye, macular pathology was present in two fellow eyes.
Conclusions: The presence of MP was confirmed in the neurosensory retina of an anatomically closed FTMH in 10 of 12 study eyes, although the levels were lower than the fellow normal macula in nine of 10 cases. This suggests a good degree of physiological recovery of photoreceptors and their axons following successful FTMH surgery.
PMCID: PMC1772824  PMID: 16113359
macular pigment; full thickness macular hole; macular hole surgery; Raman spectroscopy

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