Abstract
Purpose:
To describe the baseline characteristics of a large international cohort of patients with macular telangiectasia type 2 (MacTel Type 2) in anticipation of a longitudinal natural history study to evaluate structural and functional changes, identify potential risk factors and related outcomes.
Methods:
Images including fundus photographs, fluorescein angiograms, optical coherence tomography and fundus autofluorescence were collected. A grading system for MacTel type 2 was developed by the central reading center to evaluate lesion characteristics. Relationships between lesion characteristics and visual acuity were evaluated.
Results:
A total of 310 participants have been enrolled in the study. The mean time since diagnosis was 3 years (range 0 to 25 years). The mean age at the baseline examination was 61 ± 9 years. The mean visual acuity in the better eye was approximately 20/32 Snellen equivalents and approximately 20/50 in the worse eye. The visual acuity in the better eye of half of the participants was 20/32 or better. We found some relationships between visual acuity and lesions characteristic of MacTel Type 2.
Conclusions:
This is the first large-scale study of patients with MacTel Type 2. More than half of the patients had 20/32 or better vision in their better eye, which is a sign that decreased function in these participants may not be reflected in central visual acuity. These findings highlight the limitation of using visual acuity measurements as a measure of function and as an outcome measure in potential clinical trials in patients with MacTel Type 2.
Keywords: Idiopathic, Macular, Natural history, Telangiectasia, Visual acuity
INTRODUCTION
Idiopathic macular telangiectasis1,2,3,4 (or idiopathic juxtafoveal or perifoveal telangiectasia) (MacTel) Type 2 is characterized by retinal opacification and telangiectatic vascular changes, right-angle venules, intraretinal crystalline deposits, foveal thinning, retinal pigment epithelial hypertrophy, and intra-retinal/subretinal neovascularization. This form of telangiectasis was considered type 2, different from type 1, the aneurysmal form and from type 3, the occlusive vascular form, described by Gass.2–3 Emphasizing the rarity of the third group and including optical coherence tomography (OCT) to understand better the nature of the vascular abnormalities and their secondary effects in the macula, Yannuzzi5 recently proposed collapsing the classification to Type 1 and Type 2 macular telangiectasia (MacTel Type 2). Possibly because early changes can be difficult to detect clinically and later phases resemble age-related macular degeneration, MacTel Type 2 is probably under-diagnosed. The true prevalence of MacTel Type 2, which has previously been considered an uncommon condition, is unknown. A better understanding of the phenotype of MacTel Type 2 will assist studies of its epidemiology.
Little is known regarding the pathogenesis and natural history of patients with MacTel Type 2. To this end the Natural History Study of Macular Telangiectasia (MacTel Study) was started in 2005. The primary objectives of the MacTel Study are to enroll subjects with macular telangiectasia type 2 (MacTel Type 2) and to document structural and functional changes over a 5-year period. The research collaboration currently spans four continents (Australia, Europe, North America and Asia) and includes 23 clinical centers and 7 basic science laboratories and specialty centers.
The purpose of this article is to describe characteristics of the MacTel Study participants at baseline and to investigate associations among measures of visual acuity and MacTel Type 2 specific fundus features.
MATERIALS AND METHODS
Participants were enrolled through 22 clinical centers representing 7 countries (Australia, France, Germany, India, Israel, United States and United Kingdom). Each center was granted approval to conduct the study from its local Institutional Review Board or independent ethics committee. The MacTel eligibility criteria required the participants be at least eighteen years of age with a diagnosis of MacTel Type 2 made by the Principal Investigator of each clinical center. Exclusion criteria included (1) diabetic retinopathy with 10 or more microaneurysms and/or small retinal hemorrhages; (2) presence of other confounding ocular conditions that may complicate the evaluation of macular telangiectasia; or (3) known allergies to fluorescein. After enrollment, the diagnosis was confirmed by the MacTel Reading Center at Moorfields Eye Hospital, London, who assessed compliance with the eligibility criteria from stereoscopic color fundus photographs, fluorescein angiograms, (OCT) and/or autofluorescence (AF) (if available).
After the participant signed a consent statement, information including age, gender, self-reported race/ethnicity, smoking history, medical history including history of diabetes mellitus, and ocular history was collected through standardized questionnaires. Participants also had a comprehensive dilated ophthalmologic examination during which monocular visual acuity was measured after refraction was performed under a standardized protocol, using the Early Treatment Diabetic Retinopathy Study LogMAR visual acuity charts at a distance of 4 meters.6,7 Scoring of the test was based on the number of letters read correctly. Possible scores ranged from 0 (Snellen equivalent <20/800) to 100 (Snellen equivalent 20/12).
Graders at the MacTel Reading Center evaluated the color photographs, fluorescein angiograms (FA), OCTs and (AF) images for MacTel Type 2 features. Gradings were based on methods published in Gass and Blodi3 with addition of OCT and AF features. Color images were graded for the classic features of MacTel Type 2 such as loss of transparency at the perifoveal retina, dilated and blunted venules in the temporal retina, right angle veins, blunted veins and crystalline deposits. Late features of MacTel were also graded. These include retinal pigment epithelium (RPE) changes, retinal atrophy and subretinal neovascularization. Corresponding FA images were graded for classic changes, such as abnormal vessels temporal to foreal avascular zone (FAZ) and retinal staining in the area of abnormal vessels. Later features of the disease such as dilation of outer retinal vessels and deep leakage usually on the level of retinal pigment epithelium or the outer retina were also graded.
The OCT images were graded for central retinal thinning, inner and outer retinal cavities which resemble the fluid filled spaces of macular oedema but do not correspond with changes on fluorescein angiography. The breaks in the inner and outer segment lines and foveal detachment were also assessed. In some advanced cases serous retinal detachment with subretinal new vessels above the level of RPE could be seen.
AF images were graded based on the observation that the MacTel Type 2 patients exhibit a typical AF pattern with the loss of masking at the central fovea. Some clinical characteristics can also been seen on the AF including right angled veins and the pigment clumping around the retinal vessels.
Data Analysis and Statistical Methods
All analyses were conducted using commercially available statistical software (SAS version 8.02; SAS Institute, Cary, NC). Demographic characteristics for participants were summarized using descriptive statistics. Distributions of eye-specific baseline characteristics were summarized for all untreated eyes enrolled in the study. The agreement of scores between left and right eyes, for participants with two study eyes, was summarized by intraclass correlation coefficients while the agreement of image characteristics between left and right eyes were summarized by the weighted κ statistic. Descriptive statistics are expressed in terms of means ± standard deviation (SD) or proportions. To describe the association of MacTel Type 2 fundus features with visual acuity, the mean visual acuity was calculated using a generalized linear model and incorporating generalized estimation equations8 (GEE) to account for the correlation between eyes. P ≤ 0.05 was accepted as statistically significant given the exploratory nature of these analyses.
RESULTS
Three hundred forty-nine participants were enrolled in the study and verified to have MacTel Type 2 between November 17, 2005 and June 4, 2008. Subsequently, 39 participants were judged to not have MacTel Type 2 by the Reading Center and are not included in this analysis.
Baseline characteristics of the 310 participants are displayed in Table 1. The mean age at enrollment was 61 ± 9 years. Sixty-four percent of the participants were female and 81% identified as Caucasian. The mean body mass index (BMI) was 30 ± 6. Forty-three percent of the participants were considered obese (BMI ≥ 30). Fifty-two percent of participants noted a history of hypertension. Of the 293 participants with systolic and diastolic measurements, 45% were categorized as having high blood pressure and 42% were categorized as having prehypertension (systolic ≥ 120 mmHg or diastolic ≥ 80 mmHg). Of the 261 participants with a fasting glucose tolerance measure available, 51(20%) participants had a measure > 7 mmol/L. The mean fasting glucose tolerance was 6 ± 2 mmol/L. Approximately 28% had a history of diabetes mellitus and 11% had a history of coronary artery disease as reported by the participant. Twelve percent of the enrolled participants were currently smoking cigarettes and 38% were former smokers. The mean age of MacTel Type 2 diagnosis was 57 ± 9 years. At the time of enrollment, the mean time since diagnosis was 3 ± 4 years (range 0 to 25 years). Approximately 41% of the participants were newly diagnosed.
TABLE 1.
Demographic characteristics of MacTel Study participants at baseline (N = 310)
| Characteristic | N (%) |
|---|---|
| Age (yrs) at enrollment | |
| < 55 | 68 (22) |
| 55–59 | 68 (22) |
| 60–64 | 62 (20) |
| 65–69 | 66 (21) |
| ≥ 70 | 46 (15) |
| Mean (SD) yrs | 61 (9) |
| Gender | |
| Female | 198 (64) |
| Male | 112 (36) |
| Race | |
| Caucasian | 250 (81) |
| Non-Caucasian* | 60 (19) |
| Body Mass IndexA | |
| Normal | 47 (16) |
| Overweight | 118 (41) |
| Obese | 125 (43) |
| Mean (SD) | 30 (6) |
| History of hypertensionB | |
| No | 142 (48) |
| Yes | 151 (52) |
| High blood pressureC | |
| Normal | 39 (13) |
| Prehypertension | 123 (42) |
| High | 131 (45) |
| Systolic – Mean (SD) | 134 (16) |
| Diastolic – Mean (SD) | 79 (10) |
| History of coronary artery diseaseB | |
| No | 274 (89) |
| Yes | 34 (11) |
| History of diabetesB | |
| No | 222 (72) |
| Yes | 86 (28) |
| Fasting glucose toleranceD | |
| < 5.5 mmol/L | 135 (52) |
| 5.5 – < 7.0 mmol/L | 5 (29) |
| ≥ 7.0 mmol/L | 51 (20) |
| Mean (SD) | 6 (2) |
| Smoking statusB | |
| Never | 155 (50) |
| Former | 116 (38) |
| Current | 37 (12) |
| Age (yrs) at diagnosisE | |
| Mean (SD) yrs | 57 (9) |
| Time (yrs) since diagnosis | |
| Mean (SD) yrs | 3 (4) |
N = 290;
N = 308;
N = 293;
N = 261;
N = 308.
SD = standard deviation
Non-Caucasians include 36-Asian, 22-Other race, 1-Black/African; 1-Native Hawaiian/Pacific Islander.
Because we are interested in the natural history of the disease, the baseline ocular characteristics are based on untreated eyes. Baseline visual acuity measurements for untreated eyes are provided in Table 2. At baseline 77 participants were treated for MacTel Type 2 in at least one eye. Nineteen (25%) of the 77 participants had had both eyes treated at baseline. The percentage of treated versus untreated participants did not vary by gender or age group (data not shown). The mean visual acuity of eyes that will be followed for their natural history was 71 ± 14 letters, approximately 20/40 Snellen equivalent. Visual acuity was 20/20 or better in 16% of these eyes. Approximately half of the eyes had 20/32 or better vision. Participants’ mean visual acuity in their better eye was 77 ± 12 letters (approximately 20/32 Snellen equivalents) while the mean visual acuity in their worse eye was 65 ± 15 letters (approximately 20/50 Snellen equivalent). Mean visual acuity in the better eye did not differ by age, gender or racial category (data not shown).
TABLE 2.
Visual acuity at baseline
| Visual acuity | Better eyeA | Worse eyeA | All eyesA |
|---|---|---|---|
| (N = 290) | (N = 290) | (N = 522) | |
| Snellen equivalent | N (%) | N (%) | N (%) |
| 20/20 or better | 71 (24) | 22 (8) | 86 (16) |
| 20/25 | 51 (18) | 31 (11) | 76 (15) |
| 20/32 | 59 (20) | 35 (12) | 84 (16) |
| 20/40 | 48 (17) | 55 (19) | 89 (17) |
| 20/50 | 23 (8) | 43 (15) | 60 (11) |
| 20/62.5 | 16 (6) | 32 (11) | 45 (9) |
| 20/80 | 11 (4) | 23 (8) | 29 (6) |
| 20/100 or worse | 11 (4) | 49 (17) | 53 (10) |
| Mean (SD) | 75 (12) | 65 (15) | 71 (14) |
Includes only non-treated eyes (N = 522 eyes of 290 participants). If participant has one non-treated eye the value for that eye is included in the better and worse eye calculation.
Mean from a generalized linear model incorporating the generalized estimating equation methodology.
SD = standard deviation.
Morphologic features as measured by color fundus photography, FA, AF and OCT are summarized in Table 3. The data are summarized for all untreated eyes. Of the 446 eyes with color fundus photograph grading available, 51% had visible telangiectatic vessels, 74% had loss of retinal transparency, 33% had RPE hypertrophy, 21% had crystalline deposits, 2% had evidence of active subretinal neovascularization, 10% had chorioretinal atrophy visible either on color images (>75 micron, distinct edge, choroidal vessels visible) or on autofluorescence by showing areas of hypofluorescence; that did not correspond to the masking of pigment at the end of the vessels, 29% had blunted retinal vessels and 25% had dilated retinal vessels. A generalized linear model using the GEE methodology was used to compute the mean visual acuity accounting for the correlation between eyes. The visual acuity in eyes with RPE hypertrophy had significantly lower visual acuity compared with eyes without it (66 letters versus 72 letters, p-value: < 0.01).
TABLE 3.
MacTel Type 2 image features at baseline
| Image feature | Mean (SE) | ||
|---|---|---|---|
| N (%)A | VAB | p-valueC | |
| Color fundus photography | |||
| Visible telangiectatic vessels | 446 | ||
| Absent | 219 (49) | 69 (0.97) | |
| Present | 227 (51) | 71 (1.01) | 0.05 |
| Loss of retinal transparency | 446 | ||
| Absent | 118 (26) | 70 (1.25) | |
| Present | 328 (74) | 70 (0.89) | 0.99 |
| RPE hypertrophy | 446 | ||
| Absent | 301 (67) | 72 (0.83) | |
| Present | 145 (33) | 66 (1.35) | <0.01 |
| Crystalline deposits | 446 | ||
| Absent | 353 (79) | 71 (0.83) | |
| Present | 93 (21) | 68 (1.75) | 0.29 |
| Subretinal neovascularization | 446 | ||
| Absent | 436 (98) | 70 (0.75) | |
| Present | 10 (2) | 64 (6.86) | 0.38 |
| Atrophy | 446 | ||
| Absent | 402 (90) | 70 (0.80) | |
| Present | 44 (10) | 69 (2.39) | 0.16 |
| Blunted retinal vessels | 446 | ||
| Absent | 316 (71) | 70 (0.82) | |
| Present | 130 (29) | 70 (1.49) | 0.90 |
| Dilated retinal vessels | 446 | ||
| Absent | 333 (75) | 69 (0.83) | <0.01 |
| Present | 113 (25) | 73 (1.36) | |
| Fluorescein angiography | |||
| Hyperfluorescence | 391 | ||
| Absent | 42 (11) | 74 (1.61) | |
| Present | 349 (89) | 70 (0.86) | 0.03 |
| Depth of hyperfluorescence | 391 | ||
| Absent | 42 (11) | 74 (1.26) | |
| Level of outer capillary network | 112 (29) | 75 (1.19) | 0.71 |
| Level of inner capillary network | 37 (9) | 65 (3.73) | 0.03 |
| Level of RPE | 200 (51) | 69 (1.04) | <0.01 |
| Autofluorescence (AF) | |||
| AF pattern | 281 | ||
| Absent | 32 (11) | 76 (1.51) | |
| Present | 249 (89) | 70 (0.91) | <0.01 |
| Large area of decreased AF | 286 | ||
| Absent | 261 (91) | 71 (0.80) | |
| Present – center point not involved | 17 (6) | 65 (3.95) | 0.10 |
| Present – center point involved | 8 (3) | 37 (6.49) | <0.01 |
| Right angled vein | 286 | ||
| Absent | 130 (45) | 69 (1.51) | |
| Present | 156 (55) | 71 (1.08) | 0.40 |
| Localized decreased AF at vessel | 286 | ||
| Absent | 186 (66) | 70 (1.25) | |
| Present | 100 (35) | 69 (1.22) | 0.53 |
| OCT | |||
| OCT hyporeflective space | 493 | ||
| Absent | 234 (47) | 71 (1.04) | |
| Present—center point not involved | 101 (20) | 72 (1.38) | 0.47 |
| Present—center point involved | 158 (32) | 69 (0.98) | 0.27 |
| OCT MacTel Type 2 spectrumD | 491 | ||
| Absent | 126 (26) | 75 (1.05) | |
| Present | 365 (74) | 69 (0.80) | <0.01 |
| MacTel Type 2 severity scale | 511 | ||
| 0/1 | 16 (3) | 81 (1.86) | |
| 2 | 20 (4) | 73 (1.77) | <0.01 |
| 3 | 176 (34) | 73 (1.07) | <0.01 |
| 4 | 299 (58) | 68 (0.87) | <0.01 |
Includes non-treated eyes only.
Mean visual acuity in study eyes using generalized linear models and the generalized estimating equation (GEE) method to account for correlation between eyes.
p-value from generalized linear model compared with the reference (“No/Questionable”) group.
Defined composite variable comprised of optical coherence tomography (OCT) MacTel Type 2 characteristics (apparent foveal detachment, IS/OS PR break, loss of ONL, hyper-reflectivity, intra-retinal pigment migration, or subretinal new vessels).
MacTel - Macular Telangiectasia; N = # of eyes; SE = standard error; VA= visual acuity; RPE = retinal pigment epithelium; IS/OS= inner segment/outer segment; PR = photoreceptor; ONL= outer nuclear layer
Fluorescein angiographic characteristics in Mac Tel Type 2 included the presence, severity and extent of hyperfluorescence. Most eyes (89%) had hyperfluorescence and 51% had hyperfluorescence at the level of RPE. The mean visual acuity of eyes with hyperfluorescence was significantly lower than that of eyes without hyperfluorescence (70 vs. 74 letters, p 0.03). In addition, eyes with hyperfluorescence at the level of the capillary network or at the level of RPE had significantly lower visual acuity compared with eyes with no hyperfluorescence (Inner capillary network: 65, RPE: 69 vs. absent: 74 letters; p-value: 0.03 and < 0.01, respectively).
The presence of the MacTel Type 2 AF pattern9 (see Figure 1) defined as an increase in the central AF due to loss of masking of the background AF of the RPE by loss of masking by luteal pigment, large area of decreased AF, right angled vein, and localized decreased AF at the vessel were MacTel Type 2 characteristics assessed via autofluorescence. Because equipment was not available at all participating centers, AF grading was available for 286 eyes. The MacTel 2 AF pattern was present 89% of the eyes. The presence of a right-angled vein and localized decreased AF at the vessel were present in 55% and 35% of eyes, respectively. Approximately 9% of eyes had the presence of a large area of decreased AF (6% with center not involved and 3% with center point involved). The visual acuity of eyes with the MacTel Type 2 AF pattern was significantly lower compared with eyes without the pattern (70 letters versus 76 letters, p-value: <0.01). In addition eyes with a large area of decreased AF either with the center point involved had significantly lower visual acuity compared with eyes without a large area of decreased AF (37 letters versus 71 letters, p-value: < 0.01).
FIGURE 1.
Example of the MacTel Type 2 AF pattern defined as an increase in the central AF due to loss of masking of the background AF of the RPE by loss of masking by luteal pigment. MacTel = Macular Telangiectasia; AF = Autofluorescence; RPE = retinal pigment epithelium.
The OCT MacTel Type 2 characteristics assessed include the presence of a hyporeflective space (see Figure 2) or whether an eye had one of the six MacTel Type 2 OCT characteristics. These include: apparent foveal detachment, IS/OS PR break, hyper-reflectivity or loss of the outer nuclear layer (ONL), intra-retinal pigment migration, or subretinal neovascularization/fibrosis. Over half of the 493 eyes had a hyporeflective space on the OCT (20% with center not involved and 32% with center involved), while 74% had at least one eye with a MacTel Type 2 change on OCT. Eyes with at least one of the 6 MacTel Type 2 OCT characteristics had significantly lower mean visual acuity compared with eyes not on the spectrum (69 letters versus 75 letters, p-value: < 0.01).
FIGURE 2.
Example of the OCT MacTel Type 2 characteristic of the presence of a hyporeflective space. OCT = optical coherence tomography.
MacTel Study eyes were classified using a severity scale developed by Wai using multiple modality imaging.10 The severity scale definitions are as follows:
Severity 0: No evidence of disease (usually fellow eyes of affected individuals)
Severity 1: Mild foveal autofluorescence changes without other abnormalities
Severity 2: Mild to moderate foveal hyperauto-fluorescence with angiographic abnormalities of macular telangiectasis
Severity 3: Moderate to marked foveal hyperauto-fluorescence with angiographic abnormalities and foveal atrophy documented on OCT
Severity 4: Mixed patterns of fundus autoflurescence or marked thinning of the retina on OCT loss of photoreceptor and with accompanying RPE hyperplasia
Because of the small number of eyes available in the MacTel Study cohort with severity score 0 and 1 these scores were combined. Just over half, 59% of the eyes had a severity score of 4. As expected the visual acuity decreased significantly with increased severity score (score 2: 73 letters, score 3: 73 letters, score 4: 68 letters versus score 0/1: 82 letters; p < 0.01, for all comparisons).
For participants with two untreated eyes, there was small to moderate agreement between right and left eye visual acuity and image characteristics (Table 4). The intraclass correlation coefficient was only .20 for visual acuity. Among the image characteristics examined, the weighted κ statistic was highest for RPE hypertrophy (.61), presence of crystalline deposits (0.55) and MacTel Type 2 AF pattern (0.53), the latter two being characteristics that have come to define the disease.
TABLE 4.
Agreement of visual acuity and image features measurements between left and right non-treated eyesA
| Characteristic | Agreement (95% confidence interval) |
|---|---|
| Visual acuity | 0.20 (0.12–.28) |
| Color fundus photography | |
| Visible telangiectatic vessels | 0.33 (0.20–0.46) |
| Loss of retinal transparency | 0.26 (0.10–0.42) |
| RPE hypertrophy | 0.60 (0.47–0.73) |
| Crystals | 0.59 (0.45–0.74) |
| Neovascular changes* | — |
| Atrophy | 0.26 (0.03–0.48) |
| Blunted retinal vessels | 0.35 (0.21–0.49) |
| Dilated retinal vessels | 0.29 (0.14–0.44) |
| Fluorescein angiography | |
| Hyperfluorescence | 0.31 (0.07–0.54) |
| Depth of hyperfluorescence | 0.30 (0.16–0.44) |
| Autofluorescence (AF) | |
| AF pattern | 0.49 (0.25–0.73) |
| Large area of decreased AF | 0.45 (0.18–0.72) |
| Right angled vein | 0.55 (0.40–0.70) |
| Localized decreased AF at vessel | 0.49 (0.33–0.65) |
| OCT | |
| OCT cyst/cavity | 0.36 (0.26–0.47) |
| OCT spectrum | 0.34 (0.20–0.48) |
| MacTel Type 2 severity scale | 0.40 (0.30–0.51) |
Restricted to participants with two untreated eyes.
A kappa statistic could not be computed because of the small number of eyes with neovascular changes.
OCT = optical coherence tomography; RPE = retinal pigment epithelium.
DISCUSSION
This is the first large-scale comprehensive assessment of patients with MacTel Type 2. The mean age at enrollment into the MacTel Study was 61 years. Visual acuity was generally good in the population we studied, with more than half of the patients having 20/32 or better vision in their better eye. We also found a high prevalence of systemic disease, particularly diabetes and hypertension, in our cohort.
The good visual acuity we found contrasts with significantly impaired visual function that we have previously found in people with MacTel Type 2. We have previously reported that scores from the National Eye Institute-Visual Function Questionnaire (NEI-VFQ),11 which evaluates the vision-related quality of life, are remarkably diminished in people with MacTel Type 2, suggesting that decreased function in these participants may not be reflected in central visual acuity. Thus the NEI-VFQ may be a better way to measure outcomes than visual acuity in response to treatment in potential clinical trials.
Change in visual acuity was associated with some of the lesions common to patients with MacTel Type 2. Approximately 33% of the patients had RPE hypertrophy on color fundus photography. The mean visual acuity for patients with RPE hypertrophy was approximately 20/50 Snellen equivalents compared with 20/40 Snellen equivalents for patents without the presence of RPE hypertrophy. Hyperfluorescence on the FA was found to be present in the majority (89%) of eyes of patients with MacTel Type 2. The central visual acuity for patients with hyperfluorescence at the level of the inner capillary network or the RPE was significantly lower compared with patients without hyperfluorescence on the FA. The AF pattern has become one of the major identifying characteristics of patients with MacTel Type 2.9 Of the eyes with an available AF image, 89% exhibited the AF pattern. The mean visual acuity for these eyes was 20/40 Snellen equivalents compared with 20/32 for eyes that did not exhibit the pattern. Less than 10% of patents had a large area of decreased AF. Of these the visual acuity was markedly reduced when the center point was involved (20/200 Snellen equivalents) compared with when the center point was not involved (20/50 Snellen equivalents). Characteristics from the OCT have been used to expand the knowledge of the clinical spectrum of idiopathic macular telangiectasia including MacTel Type 2.5 In our cohort the majority of eyes (74%) had lesions that defined the OCT MacTel Type 2 Spectrum. The visual acuity for eyes on the spectrum was significantly lower compared with eyes not on the spectrum (20/40 Snellen equivalents versus 20/32 Snellen equivalents). Lastly using the recently developed MacTel severity scale we found that visual acuity was significantly lower for eyes on the upper end of scale compared with eyes on the lower end (20/50 Snellen equivalents versus 20/25 Snellen equivalents).
Although MacTel Type 2 is almost always bilateral we found that the progression of disease is not necessarily uniform as observed by the agreement measures between fellow eyes presented in Table 4. Many of the image characteristics and visual acuity used to measure disease severity had small to moderate agreement between eyes.
A high proportion of patients in this cohort had high blood pressure as determined by systolic and diastolic measurements (systolic ≥ 140 mmHg or diastolic ≥ 90 mmHg) and/or diabetes (45% and 28%, respectively). Diabetes has been linked with MacTel Type 2 in previous case reports. Green et al12,13 described the clinical and histopathologic features of MacTel Type 2. They reported the presence of retinal capillary changes in a 58 year old woman with MacTel Type 2 that were similar to those observed in the diabetic and prediabetic state. However, this patient had no history of diabetes mellitus. Although her fasting blood glucose levels on two occasions were normal, a diagnostic glucose tolerance test was not performed. This case suggests a possible relationship of diabetes mellitus with MacTel Type 2.
One group of investigators raised the hypothesis that MacTel Type 2 may be caused by abnormal glucose metabolism.14 Twenty-eight patients with this entity underwent glucose tolerance testing. Although the number of cases was small, there was a suggestion of an association, with 35% of the patients showing abnormal glucose tolerance tests. This view is also supported by the description of patients with long-standing diabetes and MacTel Type 2.15 Further studies are required to evaluate the true relationship of MacTel Type 2 with diabetes mellitus.
In addition to environmental risk factors, it appears that there may be a genetic predisposition to MacTel Type 2 in some patients. Barbazetto reported from 26%, and maybe up to 57%, of patients of European-American descent carried possibly disease-associated ataxia telangiectasia-mutated gene alleles.16 Another recent report highlighted familial transmission of MacTel Type 2, however it is not yet known to what extent this occurs.17
Strengths of this study include prospective design and data collection from the largest cohort of people with MacTel Type 2 yet assembled. A major weakness is that we are only able to report the prevalence of various systemic conditions from our population of MacTel Type 2 participants. We are currently enrolling age-matched controls as part of a genetics study. With the addition of controls we will be able to evaluate possible risk factors, including diabetes mellitus and cardiovascular disease, for MacTel Type 2 in a future report.
In conclusion, this is the first report of baseline characteristics for a large international cohort of patients with MacTel Type 2. This cohort of participants with MacTel Type 2 will now be followed to understand better the natural course of the disease and to investigate the relationships between visual acuity, potential risk factors for disease and changes in clinical findings as measured by fluorescein angiograms, optical coherence tomography and autofluorescence.
ACKNOWLEDGMENTS
This study was supported by the Lowy Medical Research Institute, LTD. The investigations were performed according to the guidelines of the Declaration of Helsinki and Institutional Review Board approval was obtained.
Footnotes
Declaration of Interest:
Participating Principal Investigators and Centers: Jose-Alain Sahel, MD, PhD, Centre Hopitalier National D’Optalmologie des Quinze-Vingts, Paris, France; Robyn Guymer, MD, Centre for Eye Research, East Melbourne, Australia; Gisele Soubrane, MD, PhD, FEBO, Clinique Ophtalmolgie de Creteil, Creteil, France; Alain Gaudric, MD, Hopital Lariboisiere, Paris, France; Steven Schwartz, MD, Jules Stein Eye Institute, UCLA, Los Angeles, CA (USA); Ian Constable, MD, Lions Eye Institute, Nedlands, Australia; Michael Cooney, MD, MBA, Manhattan Eye, Ear, & Throat Hospital, New York, NY (USA); Cathy Egan, MD, Moorfields Eye Hospital, London, England (UK); Lawrence Singerman, MD, Retina Associates of Cleveland, Cleveland, OH (USA); Mark Gillies, MD, PhD, Save Sight Institute, Sydney, Australia; Martin Friedlander, MD, PhD, Scripps Research Institute, La Jolla, CA (USA); Daniel Pauleikhoff, Prof. Dr., St. Franziskus Hospital, Muenster, Germany; Joseph Moisseiev, MD, The Goldschleger Eye Institute, Tel Hashomer, Israel; Richard Rosen, MD, The New York Eye and Ear Infirmary, New York, NY (USA); Robert Murphy, MD, The Retina Group of Washington, Fairfax, VA (USA); Frank Holz, MD, University of Bonn, Bonn Germany; Grant Comer, MD, University of Michigan, Kellogg Eye Center, Ann Arbor, MI (USA); Barbara Blodi, MD, University of Wisconsin, Madison, WI (USA); Diana Do, MD, The Wilmer Eye Institute, Baltimore, MD (USA); Alexander Brucker, MD, Scheie Eye Institute, Philadelphia, PA (USA); Raja Narayanan, MD, LV Prasad Eye Institute, Hyderabad, India; Sebastian Wolf, MD, PhD, University of Bern, Bern, Switzerland; Philip Rosenfeld, MD, PhD, Bascom Palmer, Miami, FL (USA).
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