Graefes Arch Clin Exp Ophthalmol DOI 10.1007/s00417-013-2346-z

RETINAL DISORDERS

Long-term course in type 2 idiopathic macular telangiectasia Tobias Meyer-ter-Vehn & Sina Herzog & Marc Schargus & Winfried Göbel & Rainer Guthoff

Received: 14 February 2013 / Revised: 22 March 2013 / Accepted: 2 April 2013 # Springer-Verlag Berlin Heidelberg 2013

Abstract Introduction To study the long-term course in patients with idiopathic macular telangiectasia and report the effect of anti VEGF and laser treatment. Methods A retrospective case series of 19 patients/38 eyes with symptomatic type 2 idiopathic macular telangiectasia was performed. Six eyes received intravitreal injections of bevacizumab (1–3 injections), four eyes received focal laser treatment. Follow up examinations comprised visual acuity, biomicroscopy, fluorescein angiography and assessment of macular morphology and thickness by time and spectraldomain optical coherence tomography (OCT). Results Mean follow-up time was 81 months (range 15– 188 months) – the median added up to 80 months. Visual outcome at final visit varied substantially (20/200–20/20). On average visual acuity decreased 1,2 lines (range −0,5 to 6) by 3 years, 2 lines (range −0,5 to 7) by 5 years and 4,1 lines (range 0 to 12) by 10 years. Development of choroidal neovascularisation was observed in only one eye. There was no significant difference in visual acuity between eyes receiving no treatment, intravitreal bevacizumab or laser treatment after 3 and 5 years. Morphological studies by OCT revealed typical changes with retinal atrophy and intraretinal cysts. Visual acuity correlated with the eccentricity of the

T. Meyer-ter-Vehn (*) : S. Herzog : W. Göbel Department of Ophthalmology, University of Wuerzburg, Josef-Schneider-Str. 11, 97080 Wuerzburg, Germany e-mail: [email protected] R. Guthoff Department of Ophthalmology, University of Duesseldorf, 40225 Duesseldorf, Germany M. Schargus Department of Ophthalmology, University of Bochum, 44892 Bochum, Germany

main manifestation–visual preservation was associated with mainly extrafoveal disease manifestation. Discussion Type 2 idiopathic macular telangiectasia is a chronic, often slowly progressing macular disease leading to retinal atrophy and visual impairment over decades. Thorough knowledge about the long term course of this disease is necessary to evaluate possible therapeutic options in the long run. Keywords Idiopathic macular telangiectasia . Idiopathic juxtafoveal telangiectasia . Long-term follow up . Bevacizumab . Avastin . Intravitreal injection . Anti VEGF treatment

Introduction Idiopathic macular telangiectasia type 2 (IMT2) is a bilateral macular disease of unknown origin with bilateral occult parafoveal telangiectasia, located predominantly in the temporal macular region causing a late phase leakage on fluorescein angiography (FA) [1]. The structural macular changes such as neuroretinal atrophy, macular cysts, alteration especially of the outer retinal architecture and reduced macular pigment can be visualized by optical coherence tomography (OCT), fundus autofluorescence and confocal blue reflectance imaging [2–6]. These parafoveal changes may result in paracentral scotoma, which cause impaired reading ability [7, 8] and when reaching the fovea reduce visual acuity. Apart from the atrophic changes of the central retina, the course of the disease can be complicated by secondary neovascularisation membranes, considered as the proliferative stage of the disease [9]. Previous treatment approaches comprised focal laser treatment, photodynamic therapy [10, 11] or more recently intravitreal VEGF inhibitors. Although the latter

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one has been studied in a couple of small case series and one randomized clinical trial (RCT) [2, 12–19], the results remained inconclusive and failed to prove longterm effectiveness. One major issue in these therapeutic studies is the time scale. While most of these studies had follow up times of 1 to 3 years, non proliferative type 2 IMT leads to slowly progressive macular atrophy and visual impairment over decades. Due to the infrequency of this disease, data on its long-term course is still sparse. Here we report the long-term course (mean follow-up time 81 months/range 15–188 months) of 19 patients/38 eyes with nonproliferative type 2 idiopathic macular telangiectasia with respect to visual acuity as well as structural changes evaluated by fundoscopy and optical coherence tomography (OCT).

Patients and methods We reviewed the charts of 19 patients (38 eyes) diagnosed as type 2 IMT between 1990 and 2012 at the university eye hospital at Wuerzburg. Diagnosis was based on fundoscopic findings (parafoveal gray opacification, right angle venules, intraretinal pigment plaques, retinal crystalline deposits), FA (telangiectatic vessels predominantly temporal to the fovea) and optical coherence tomography (OCT) when available. Visual acuity was measured at 5 m using standardized visual acuity charts. For statistical work-up visual acuity measurements were converted to logMAR scale. FA was performed using a digital fundus camera (Zeiss FF450, Carl Zeiss Meditec, Jena, Germany). Retinal thickness and architecture was examined using optical coherence tomography. Due to the long time scale of this chart review, different OCT systems were employed (STRATUS OCT & Cirrhus SD-OCT, Carl Zeiss Meditec GmbH, Jena, Germany; Spectralis SD-OCT, Heidelberg Engineering, Heidelberg, Germany). In order to analyse changes of retinal morphology we took care to compare measurements from the same system– mainly the STRATUS OCT–as available. Macular thickness map protocol offered by STRATUS OCT was used to obtain 6 consecutive radial 6 mm scans centered on the fovea. Central retinal thickness (CRT) was defined as the distance between the inner limiting membrane and the surface of the high-reflective RPE/choriocapillaris layer–computed values were used. With spectral domain OCT (Cirrus SD-OCT, Spectralis SD-OCT) macular volume scans were obtained– the built-in algorithm for retinal thickness determination was used. For laser treatment a frequency doubled YAG-laser with 532 nm wavelength was employed.

Intravitreal injections of 1.25 mg bevacizumab/0.05 ml were administered according to the guidelines of the German Ophthalmological Society. Informed written consent including the “off label” character of this treatment modality was obtained from each patient. Follow up examination was scheduled 8 weeks after the initial intravitreal injection. Reinjection was considered when FA showed persistent leakage or when visual acuity decreased.

Results Demographic profile The mean age was 57.2±8.4 years (range, 41–73 years)– there were 10 male patients and 9 female patients (Table 1). The mean follow-up time was 81 months (range 15– 188 months)–the median follow-up time added up to 80 months. From the 19 patients included in our observation 16/13/10/5 patients had a follow-up time of at least 3/5/7/10 years, respectively. Baseline examination Visual acuity (VA) at baseline ranged from logMAR −0,08 to 1,0 (Snellen 20/200 to 20/16)–mean VA was 0,18±0,22 (snellen 20/30) with a median of 0,1 (snellen 20/25) (Table 2). The main reason for poor VA at baseline was retinal atrophy compatible with advanced type IMT. OCT examination showed typical intraretinal cysts in the inner and outer retina. On Stratus OCT examination central retinal thickness (CRT) in our cohort was reduced to 173±35 μm (mean ± standard deviation/SD; range 132 μm–228 μm) compared with reported 213± 19 μm in healthy subjects [20]–for Cirrhus measurements CRT was reduced to 228±30 μm (mean ± SD; range 208 μm–255 μm) compared with 276±17 μm in healthy subjects. Visual acuity Mean visual acuity deteriorated over time–mean visual acuity loss increased from 0,041 logMAR units loss (equivalent to 0,41 lines of visual acuity) after 1 year to 1,2 lines after 3 years, 2,0 lines after 5 years and 2,2 lines after 7 years to finally 4,1 lines after 10 years (Fig. 1a). As the absolute number of eyes was limited, median visual acuity loss with respective quartiles was evaluated as well (Fig. 1a). Moreover absolute visual acuity decreased from logMAR 0,218 (snellen 20/33) after 1 year to logMAR 0,25 (snellen 20/35) after

Graefes Arch Clin Exp Ophthalmol Table 1 Patients’ characteristics Patient

Age

Sex

1

40,9

F

Last visit VA

Follow up [mth]

Δ lines

Δ lines/yr

OD

20/20

20/30

55,9

−1,5

−0,33

20/20 20/25 20/25 20/40 20/25 20/50 20/25 20/30 20/25 20/30 20/25 20/25 20/30 20/40 20/30 20/20

20/25 20/30 20/50 20/30 20/20 20/200 20/25 20/400 20/120 20/40 20/30 20/60 20/50 20/200 20/100 20/20

40,3

−0,5 −1,2 −3,5 1,5 0,5 −6,0 −1,0 −11,5 −7,0 −1,5 −1,2 −4,3 −1,8 −7,0 −4,8 0,0

−0,10 −0,13 −0,37 1,16 0,36 −1,65 −0,27 −0,84 −0,51 −0,91 −0,78 −1,28 −0,53 −0,64 −0,43 0,00

187,8

3,0 −3,0

0,90 −0,19

0,5 −4,0 −1,0 −3,0 −2,6 −2,0 −0,8 0,0 0,0 −3,0 0,0 −3,0 0,5 −3,0 −0,6 −1,8 −2,2 0,5

0,03 −0,46 −0,11 −0,23 −0,19 −0,29 −0,11 0,00 0,00 −0,44 0,00 −0,62 0,09 −2,04 −0,39 −0,24 −0,30 0,08

−1,9

−0,29

2

48,2

M

3

62,9

M

4

53,7

F

5

57,9

M

6

48,9

F

7

56,0

M

8

62,8

M

9

53,8

M

OS OD OS OD OS OD OS OD OS OD OS OD OS OD OS OD

F

OS OD

20/200 20/20

20/100 20/40

OS OD OS OD OS OD OS OD OS OD OS OD OS OD OS OD OS OD

20/25 20/20 20/20 20/20 20/25 20/25 20/16 20/60 20/40 20/100 20/40 20/50 20/25 20/50 20/25 20/30 20/20 20/25

20/20 20/50 20/25 20/40 20/40 20/40 20/20 20/60 20/40 20/200 20/40 20/100 20/20 20/100 20/30 20/50 20/30 20/25

OS

20/25

20/60

10

Visual acuity is stated in snellen fraction. Lines represent visual acuity lines gain/loss. OD right eye. OS left eye. PC photocoagulation. IVB intravitreal bevacizumab. Treated und untreated patients

Baseline VA

52,0

11

47,8

M

12

57,4

F

13

48,9

M

14

59,8

F

15

55,1

F

16

71,7

F

17

72,7

M

18

63,2

M

19

73,0

F

3 years, logMAR 0,3 (snellen 20/40) after 5 years to finally logMAR 0,34 (snellen 20/44) after 10 years (Fig. 1b). Both the number of lost lines and the course of absolute visual acuity showed a marked variability. Visual acuity at final visit was logMAR 0,39±0,34 (snellen 20/50, range 20/400 to 20/20)–16 of 38 eyes (42 %) had a VA below 20/40, 5 eyes (13 %) 20/200 or worse (Table 2). One eye (patient 16) developed

113,0 15,1 43,7 164,1 19,3 40,0 131,7

103,6 160,2 83,5 63,1 81,3 58,0 17,7 89,4 80,1

Treatment

PC PC, IVB IVB 2x

PC

PC

IVB 1x IVB 3x IVB 2x IVB 1x

choroidal neovascularization (CNV) after 5 years (3 %), resulting in a visual decline to logMAR 1,3 (snellen 20/400). Morphological changes OCT examination revealed cavities in the inner and outer retina as typical features of IMT. These cavities

Graefes Arch Clin Exp Ophthalmol Table 2 Detailed information on visual acuity course Time [mths]

n

Visual acuity [logMAR]

Absolute

Proportion

Mean

SD

Median

Min

Max

<20/40

≤20/100

≤20/200

<20/40

≤20/100

≤20/200

First visit 6 12 18 36

38 38 38 38 32

0,18 0,19 0,22 0,25 0,29

0,22 0,23 0,24 0,26 0,28

0,10 0,14 0,16 0,16 0,25

−0,1 −0,1 −0,1 −0,1 0,0

1,0 1,0 1,0 1,0 1,0

6 7 8 10 12

2 2 2 3 3

1 1 1 1 2

0,16 0,18 0,21 0,26 0,38

0,05 0,05 0,05 0,08 0,09

0,03 0,03 0,03 0,03 0,06

60 84 120 Final visit

26 20 10 38

0,35 0,35 0,50 0,39

0,31 0,32 0,41 0,34

0,30 0,26 0,34 0,30

0,0 0,0 0,0 0,0

1,0 1,0 1,3 1,3

10 8 5 16

5 4 2 9

1 1 2 5

0,38 0,40 0,50 0,42

0,19 0,20 0,20 0,24

0,04 0,05 0,20 0,13

often remained constant over years with only modest response to anti-VEGF treatment. Figure 2a displays these cysts in the inner retina in patient 15, who received photocoagulation for both eyes at baseline and three bevacizumab injections 2 years later in his right eye. Neither photocoagulation nor bevacizumab injection caused marked changes of these cysts. Over time, patient 15 also developed cysts in the outer retina and retinal thinning predominantly in the temporal macular region in his right eye; this led to further visual acuity

loss (Fig. 2b). His left eye showed enlargement of the inner retina cavity as well as development of an extrafoveal outer retinal cyst while visual acuity in this eye remained constant. Analysis of structural changes associated with low visual acuity revealed two risk factors: first, development of pigment hypertrophy (Gass stage 4) [21] often combined with cysts in the outer retina, general thinning of the retina and loss of normal retinal architecture. Second, the proximity of retinal lesions to the fovea– patient 10 preserved a reasonable visual acuity over 15 years but complained about reading problems due to paracentral scotoma resulting from parafoveal hyperpigmented lesions (Fig. 3). Effect of treatment modalities

Fig. 1 Long-term course of visual acuity–a represents relative change of visual acuity from baseline (gained/lost lines) at different time points as a box plot. Moreover the sample size at the respective time points is stated. b shows absolute visual acuity measurements at respective time points as a box blot

Six eyes from six patients were treated with bevacizumab injections (mean 1.7–range 1 to 3). All intravitreal injections were performed without complications, particularly no endophthalmitis or retinal detachment. Fluorescein leakage decreased temporally to the fovea after bevacizumab injection in all eyes but recurred after 3–5 months as shown as an example in patient 14 (Fig. 4). As mentioned above, there were no marked structural changes (CRT, number and size of intraretinal cysts) observed by OCT examination. Visual acuity 3 years after bevacizumab injection remained stable in two patients (patient 14 and 15) at a low level (logMAR 0,8 and 0,5/snellen 20/120 and 20/60 respectively). Patient 16 suffered another 3 lines of visual loss from logMAR 0,4 to 0,7 (snellen 20/50 to 20/100) and developed subretinal neovascularisation 4 years after injection in the same eye. Figure 5 summarizes the visual acuity change at 3 years (Untreated: mean −1,2±1,5 lines; Avastin: mean −1,0±1,8 lines; photocoagulation mean −1,9±1,9 lines)

Graefes Arch Clin Exp Ophthalmol Fig. 2 Sequential OCT scans (6 mm horizontal scans) from patient 15. Patient 15 received three bevacizumab injections 2 years after first admission– injections were ceased since no improvement both subjective and regarding visual acuity and OCT scans could be achieved. During the initial 4 years intraretinal cysts remained constant (a). Three years after the injections, intraretinal cysts enlarged, also encompassing the outer retina (b) in the treated and untreated eye

and 5 years (Untreated: mean −2,0±2,4 lines; photocoagulation mean −2,8±2,2 lines) of follow-up. There is a considerable overlap between groups treated with photocoagulation or bevacizumab and untreated eyes. The data does not suggest a significant benefit of laser treatment or bevacizumab injections.

Discussion IMT type 2 are characterised by parafoveolar located telangiectatic vessels, showing fluorescein leakage on angiography, and atrophic changes predominantly of the temporal macular with thinning of the neurosensory retina and intraretinal cysts [2, 4, 21, 22]. Although known for over three decades this entity remains obscure in various respects–neither the pathophysiology nor the natural course of this disease is understood in detail so far.

After a first classification by Gass and Oyakawa in 1982, Gass and Blodi revised and refined the previous classification in a report of a large IMT type 2 cohort comprising 72 patients/144 eyes with a follow up time of at least 2 years (mean 91 months) [21, 22]. They reported that a third of the patients preserved a VA of 20/30 or better in at least one eye, but 25 % of the eyes worsened to 20/200 and below. Unfortunately, detailed information on the course of visual acuity is missing. Another long-term study (follow up 10–19 years) reported substantial loss of vision in 18 of 24 eyes (75 %) due to hyperpigmented lesions and subretinal neovascularisation. Again, detailed information on the course of visual acuity is missing and morphological changes were shown only exemplarily [23]. Recently, Shukla et al. reported on a cohort of 104 patients/203 eyes with IMT type 2 with a median follow-up time of 21 months (range 12–156 months) [24]. They included

Graefes Arch Clin Exp Ophthalmol Fig. 3 Long-term follow up of IMT type 2 patients–both patients developed hyperpigmented lesions temporal to the fovea with outer retina cysts on OCT scans. While patient 10 preserved good visual acuity, patient 5 suffered severe visual loss. Despite good visual acuity patient 10 complained about reading problems due to deep paracentral scotomas

data on visual acuity at 1 and 2 year follow-up and at the final visit, but no data on 5 years or 10 years follow-up was shown. The prognosis of patients with IMT type 2 remains unclear. While short term and cross sectional studies suggest a moderate to good prognosis for preservation of visual acuity [25] long-term reports come to different conclusions Fig. 4 Patient 14 showed a temporary decrease of late stage fluorescein leakage–the figure depicts fluorescein angiography before (upper panel), 3 months (middle panel) and 6 months (lower panel) after intravitreal bevacizumab injection

[21, 23]. This discrepancy may suggest that IMT type 2 is a slowly progressing disease with a time frame of several years to decades. Here we report on a cohort of 19 patients/38 eyes diagnosed for IMT type 2 with a mean follow up time of 81 months (range 15–188 months) and detailed information on the course of visual acuity after 5, 7 and 10 years.

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Fig. 5 Change in visual acuity from baseline at 3 and 5 years follow up in patients who received photocoagulation (PC), intravitreal bevacizumab (IVB) or no treatment (no Tx)

Mean visual acuity at baseline (logMAR 0,18±0,22) in our cohort was slightly better than in the larger sample reported by Shukla and coworkers with a visual acuity of 0,31±0,24 (logMAR, non proliferative type) and Watzke and coworkers with 0,30±0,23 (logMAR) [23, 24]. It is remarkable that we observed a development of the proliferative stage of IMT in only one eye (3 %) compared to other reports with incidence figures of 14 % [24] and up to 33 % [23]. On average, visual acuity deteriorated 0,5 lines after 1 year, 0,7 lines after 18 months and 1,2 lines after 3 years, which is in agreement with data reported by Shukla et al. [24]. Mean visual acuity at final visit was 0,39 ± 0,34 (logMAR) in line with numbers reported by Shukla et al. in his nonproliferative cohort (0,36±0,26). In our stu,dy the proportion of eyes below 0,3 (logMAR) [20/40] was 41 % (Shukla et al. 44 %) and the number of eyes below 1.0 (logMAR) [≤20/200] after 10 years of follow-up was 20 %, similar to the percentage reported by Gass et al. (26 %–37 out of 144 eyes) [21]. The course of visual acuity after 3, 5, 7 and 10 years in our study suggests that non-proliferative IMT type 2 is a slowly progressive disease with ongoing visual deterioration over several years or even decades. After 10 years median vision loss added up to 3,4 lines (range 0–11 lines). Median visual acuity at this time point of time was 20/45 (range 20/320 to 20/20) and the percentage of eyes below 20/40 increased to 50 %, the percentage below 20/200 to 20 %. Intravitreal bevacizumab injection caused a temporary reduction of late phase staining in fluorescein angiography with a rebound 4–8 weeks post injection as observed in other studies [17]. We did not observe a marked decrease of intraretinal cysts or retinal thickness after intravitreal bevacizumab injection contrary to other studies with monthly administered ranibizumab demonstrating a moderate decrease of retinal thickness especially in the temporal macular region by 10–15 % [17, 19]. The difference may be

explained by the retrospective non-interventional nature of our study and the small number of injections (1–3). With regard to visual acuity we found neither a short- nor a long-term benefit from intravitreal bevacizumab at 3 years of follow-up. Promising small case series showing visual acuity improvement with anti-VEGF injections [12, 16] during follow-up periods from 1 to 3 years could not be confirmed in two small controlled trials with monthly ranibizumab injections [17, 19]. To summarize, intravitreal VEGF blockade leads to a decrease of fluid extravasation from telangiectatic vessels probably associated with a moderate decrease of retinal thickness with frequent reinjections [17, 19], but does not significantly improve visual acuity. The long-term OCT series of patient 15 in our cohort may shed light on another interesting finding. While the growth of a foveal intraretinal cyst in the inner retina was not associated with a decrease in visual acuity, development of an outer retinal cyst was accompanied by further visual deterioration. This phenomenon has been described in more detail by Charbel Issa et al., who demonstrated that the integrity especially of the outer retinal layers is important for light perception [26]. We observed these outer retina layer disturbances in patients with a long standing IMT type 2 disease. Visual impairment in long-term IMT type 2 patients depends significantly on the distance between the lesion focus and the fovea. Although some patients with parafoveolar lesions preserved good visual acuity they still complained of reading problems. A microperimetry study in a large cohort of IMT type 2 patients revealed that the main decrease in light sensitivity corresponds well with the parafoveal lesion focus in IMT type 2 [7]. Therefore one should reconsider visual acuity as the primary endpoint parameter in IMT type 2 therapeutic intervention studies, and consider replacing or complementing it with central visual field results. Unfortunately this data is mostly missing in our retrospective study. In sum, we report in detail on the long-term course of 38 eyes of 19 patients with type 2 IMT, trying to bridge the gap between short term and cross sectional studies with often reasonable visual outcome and poor results from long-term reports [21, 23]. Our data, although small in size, indicates clearly that non-proliferative IMT type 2 is associated with a progressive visual decline over at least a decade, shifting the time frame for interventional studies from years to a decade. Both intravitreal bevacizumab injection and laser treatment did not improve visual outcome. As far as morphology is concerned, cysts in the inner retina are followed by cysts in the outer retina, probably associated with a significant loss of light sensitivity. Long-term observational studies as initiated by the Mac Tel project [27] are necessary to better understand the natural course of the disease and better evaluate the significance and efficacy of respective therapeutic interventions.

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References 1. Charbel Issa P, Gillies MC, Chew EY, Bird AC, Heeren TF, Peto T, Holz FG, Scholl HP (2012) Macular telangiectasia type 2. Prog Retin Eye Res epub ahead doi:10.1016/j.preteyeres.2012.11.002 2. Charbel Issa P, Holz FG, Scholl HP (2007) Findings in fluorescein angiography and optical coherence tomography after intravitreal bevacizumab in type 2 idiopathic macular telangiectasia. Ophthalmology 114:1736–1742 3. Surguch V, Gamulescu MA, Gabel VP (2007) Optical coherence tomography findings in idiopathic juxtafoveal retinal telangiectasis. Graefes Arch Clin Exp Ophthalmol 245:783–788 4. Gaudric A, Ducos de Lahitte G, Cohen SY, Massin P, Haouchine B (2006) Optical coherence tomography in group 2A idiopathic juxtafoveolar retinal telangiectasis. Arch Ophthalmol 124:1410–1419 5. Helb HM, Charbel Issa P, van der Veen RL, Berendschot TT, Scholl HP, Holz FG (2008) Abnormal macular pigment distribution in type 2 idiopathic macular telangiectasia. Retina 28:808–816 6. Charbel Issa P, Finger RP, Helb HM, Holz FG, Scholl HP (2008) A new diagnostic approach in patients with type 2 macular telangiectasia: confocal reflectance imaging. Acta Ophthalmol 86:464–465 7. Charbel Issa P, Helb HM, Rohrschneider K, Holz FG, Scholl HP (2007) Microperimetric assessment of patients with type 2 idiopathic macular telangiectasia. Investig Ophthalmol Vis Sci 48:3788–3795 8. Finger RP, Charbel Issa P, Fimmers R, Holz FG, Rubin GS, Scholl HP (2009) Reading performance is reduced by parafoveal scotomas in patients with macular telangiectasia type 2. Investig Ophthalmol Vis Sci 50:1366–1370 9. Yannuzzi LA, Bardal AM, Freund KB, Chen KJ, Eandi CM, Blodi B (2006) Idiopathic macular telangiectasia. Arch Ophthalmol 124:450–460 10. Park DW, Schatz H, McDonald HR, Johnson RN (1997) Grid laser photocoagulation for macular edema in bilateral juxtafoveal telangiectasis. Ophthalmology 104:1838–1846 11. De Lahitte GD, Cohen SY, Gaudric A (2004) Lack of apparent short-term benefit of photodynamic therapy in bilateral, acquired, parafoveal telangiectasis without subretinal neovascularization. Am J Ophthalmol 138:892–894 12. Charbel Issa P, Finger RP, Holz FG, Scholl HP (2008) Eighteenmonth follow-up of intravitreal bevacizumab in type 2 idiopathic macular telangiectasia. Br J Ophthalmol 92:941–945 13. Charbel Issa P, Scholl HP, Holz FG (2007) Intravitreal bevacizumab for the treatment of type 2 idiopathic macular teleangiectasis. Retin Case Brief Rep 1:189–191 14. Kovach JL, Rosenfeld PJ (2009) Bevacizumab (avastin) therapy for idiopathic macular telangiectasia type II. Retina 29:27–32

15. Matsumoto Y, Yuzawa M (2010) Intravitreal bevacizumab therapy for idiopathic macular telangiectasia. Jpn J Ophthalmol 54:320–324 16. Matt G, Sacu S, Ahlers C, Schutze C, Dunavoelgyi R, Prager F, Pruente C, Schmidt-Erfurth U (2010) Thirtymonth follow-up after intravitreal bevacizumab in progressive idiopathic macular telangiectasia type 2. Eye (Lond) 24:1535–1541 17. Charbel Issa P, Finger RP, Kruse K, Baumuller S, Scholl HP, Holz FG (2011) Monthly ranibizumab for nonproliferative macular telangiectasia type 2: a 12-month prospective study. Am J Ophthalmol 151:876–886 18. Roller AB, Folk JC, Patel NM, Boldt HC, Russell SR, Abramoff MD, Mahajan VB (2011) Intravitreal bevacizumab for treatment of proliferative and nonproliferative type 2 idiopathic macular telangiectasia. Retina 31:1848–1855 19. Toy BC, Koo E, Cukras C, Meyerle CB, Chew EY, Wong WT (2012) Treatment of nonneovascular idiopathic macular telangiectasia type 2 with intravitreal ranibizumab: results of a phase II clinical trial. Retina 32:996–1006 20. Wolf-Schnurrbusch UE, Ceklic L, Brinkmann CK, Iliev ME, Frey M, Rothenbuehler SP, Enzmann V, Wolf S (2009) Macular thickness measurements in healthy eyes using six different optical coherence tomography instruments. Investig Ophthalmol Vis Sci 50:3432–3437 21. Gass JD, Blodi BA (1993) Idiopathic juxtafoveolar retinal telangiectasis. Update of classification and follow-up study. Ophthalmology 100:1536–1546 22. Gass JD, Oyakawa RT (1982) Idiopathic juxtafoveolar retinal telangiectasis. Arch Ophthalmol 100:769–780 23. Watzke RC, Klein ML, Folk JC, Farmer SG, Munsen RS, Champfer RJ, Sletten KR (2005) Long-term juxtafoveal retinal telangiectasia. Retina 25:727–735 24. Shukla D, Gupta SR, Neelakantan N, Tiwari S, Gupta S, Patwardhan AR, Soubhya TB (2012) Type 2 idiopathic macular telangiectasia. Retina 32:265–274 25. Chew EY (2006) Parafoveal teleaniectasis. In: Ryan SJ, Hinton DR, Schachat AP, Wilkinson CP (eds) Retina. Mosby, St. Louis, pp 1409–1415 26. Charbel Issa P, Troeger E, Finger R, Holz FG, Wilke R, Scholl HP (2010) Structure-function correlation of the human central retina. PLoS One 5:e12864 27. Clemons TE, Gillies MC, Chew EY, Bird AC, Peto T, Figueroa MJ, Harrington MW (2010) Baseline characteristics of participants in the natural history study of macular telangiectasia (MacTel) MacTel Project Report No. 2. Ophthalmic Epidemiol 17:66–73