Idiopathic macula telangiectasia (IMT) is characterized by retinal capillary vessel dilation. In 1982, Gass and Owaka proposed a classification of IMT, termed idiopathic juxtafoveal retinal telangiectasis.1 In 2006, Yannuzzi et al2 classified three types: Type 1 IMT (aneurysmal telangiectasia), Type 2 IMT (perifoveal telangiectasia), and Type 3 IMT (occlusive telangiectasia).
Type 1 IMT is unilateral and relatively common in Japanese men.3 It predominantly occurs in middle-aged men and is typically located in the temporal half of the macula. The condition may lead to visual loss because of the occurrence of macular edema with hard exudates. Telangiectasia is generally confined unilaterally in the perifoveal area, 1 to 2 discs in diameter, involving equivalent areas superior and inferior to the horizontal raphe. Multiple, venular, and arteriolar aneurysms can occur in cases of superficial ischemia and lipid deposition. Visual loss is mainly caused by macular edema and hard exudation.3,4 There is no established treatment for Type 1 IMT. Although laser photocoagulation (LP), sub-Tenon's capsule injection of triamcinolone acetonide, dexamethasone intravitreal implant, and intravitreal anti–vascular endothelial growth factor (VEGF) have been proposed as potentially effective treatment procedures,5–10 to the best of our knowledge, only case reports of short-term observations have been published.
Moreover, the pathogenesis, long-term ocular adverse events, and relationship with systemic medical history of Type 1 IMT remain unclear. Therefore, the aim of this retrospective case series was to examine the clinical features of treated (LP and/or intravitreal anti-VEGF) and untreated Type 1 IMT eyes over a 2-year follow-up period.
Study Design and Participants
This study was approved by the Ethics Committee at Kagawa University Faculty of Medicine and conducted in accordance with the tenets of the Declaration of Helsinki. In this retrospective case series, clinical records and photographic files from the Kagawa University Hospital were reviewed to identify patients diagnosed with Type 1 IMT between November 2007 and April 2012.
All identified patients (n = 49) underwent best-corrected visual acuity (BCVA) examinations, fluorescein and indocyanine angiography (HRA2; Heidelberg Engineering, Heidelberg, Germany), fundus photography (Optos 200Tx imaging system; Optos PLC, Dunfermline, United Kingdom), and optical coherence tomography (Spectralis HRA + OCT; Heidelberg Engineering).
All eyes of 49 patients with Type 1 IMT were treatment naive, with retinal microvascular telangiectasia, parafoveal venular and arteriolar aneurysms, superficial ischemia, cystoid macula edema (CME), and lipid deposition observed with fundus color, angiographic photographs, and optical coherence tomography. Patients with secondary macular telangiectasia (e.g., venous occlusion, diabetic retinopathy, and Coat disease) and neovascular maculopathy (e.g., age-related macular degeneration, retinal angiomatous proliferation, pathologic myopia, and angioid streaks) were excluded.
At the initial visit, eyes with a Snellen BCVA of 20/33 or less or a central retinal thickness (CRT) of at least 350 μm were treated, whereas the remaining eyes were observed without treatment. As the initial treatment, a focal Argon LP was performed on the perifoveal area about the central avascular area of the fovea, targeting the retinal microaneurysm (MA). Laser photocoagulation was performed using a yellow wavelength, power of 80 mW to 120 mW, spot size of 50 μm to 150 μm, and duration of 0.15 seconds to 0.2 seconds using Novus Varia (Lumenis, Santa Clara, CA). In cases where laser treatment would be difficult due to the proximity of the retinal MA to the fovea, intravitreal bevacizumab (IVB) (Avastin; Genentech, San Francisco, CA) of 1.25 mg was administered.
Study Procedures and Examinations
Changes in BCVA and CRT were examined in all patients 1 month after treatment. If the BCVA worsened, and the CRT did not reduce, additional treatments were administered. If the CRT reduced, patients were examined monthly and retreated, if necessary. The retreatment criteria were as follows: BCVA reduction by more than 2 lines, CRT increased by more than 50 μm, and occurrence of persistent CME.11 All patients were fully informed about the off-label use of bevacizumab and its potential side effects. In addition, patients' systemic history and occurrence of any retinal vascular adverse events during the follow-up period were examined.
A Statistical analysis of changes in the logarithm of the minimum angle of resolution (logMAR) BCVA and CRT between baseline (initial visit) and 24 months was performed by paired t test. Longitudinal analysis using a generalized estimating equation was also conducted to evaluate the influence of retinal vascular events. Potential confounding factors, including sex, initial CRT and logMAR BCVA, and systemic medical history (such as cerebral infarction and myocardial infarction) were included in the modeling. Significant influencing factors of retinal vein occlusion (RVO) were examined using Fisher's exact probability test. Statistical analysis was used with SPSS software version 20.0 (IBM Corp, Armonk, NY). P values <0.05 were considered statistically significant.
Forty-nine treatment-naive patients with unilateral Type 1 IMT (29 men, 20 women; mean ± SD age, 70.5 ± 11.6 years) were included in this study. The follow-up periods exceeded 24 months in all patients. Patient baseline characteristics are summarized in Table 1. At baseline, all eyes showed prominent parafoveal capillaries, MAs, and CME. For all patients, fluorescein angiography showed late leakage surrounding the fovea, whereas optical coherence tomography revealed CME. Of 49 eyes, 9 were treated with LP monotherapy, 12 with LP and IVB, 10 with IVB monotherapy, whereas the remaining 18 eyes did not receive any treatment.
Systemic Medical History of Patients With Type 1 Idiopathic Macula Telangiectasia
The systemic medical histories were as follows: blood hypertension in 22 patients (44.9%), hyperlipidemia in 13 patients (26.5%), cerebral infarction in 7 patients (14.3%), and myocardial infarction in 4 patients (8.2%) (Table 1).
Change in logMAR Visual Acuity
The mean logMAR BCVA was 0.20 ± 0.19 (median, 20/29) and 0.13 ± 0.22 (median, 20/25) at baseline and 24 months (P = 0.023), respectively (Table 2). The mean logMAR BCVA according to the treatment option was as follows: LP alone, 0.23 ± 0.18 (median, 20/33) and 0.16 ± 0.14 (median, 20/31); LP with IVB, 0.32 ± 0.18 (median, 20/40) and 0.25 ± 0.23 (median, 20/33); IVB alone, 0.20 ± 0.11 (median, 20/33) and 0.16 ± 0.32 (median, 20/25); and nontreatment, 0.11 ± 0.16 (median, 20/22) and 0.03 ± 0.13 (median, 20/21), at baseline and 24 months, respectively. In each treatment group, there were no significant differences between baseline and 24 months (Figure 1). The logMAR BCVA improved in seven eyes (14%; LP alone, one eye; IVB with LP, 4 eyes; nontreatment, 2 eyes), maintained in 41 eyes (84%; LP alone, 8 eyes; IVB with LP, 8 eyes; IVB alone, 9 eyes; nontreatment, 16 eyes), and decreased in one eye (2%; IVB alone), when a logMAR BCVA >0.3 was defined as a meaningful change.
Change in Central Retinal Thickness
The mean CRT of treated eyes was 375.0 ± 94.5 μm and 315.3 ± 78.5 μm at baseline and 24 months (P < 0.001), respectively (Table 2). According to the treatment option, the mean CRT was as follows: LP alone, 350.2 ± 62.6 μm and 296.4 ± 90.1 μm; LP with IVB, 485.6 ± 97.3 μm and 389.8 ± 88.3 μm; IVB alone, 362.8 ± 49.9 μm and 291.2 ± 56.9 μm; nontreatment, 321.1 ± 60.9 μm and 288.2 ± 34.7 μm, at baseline and 24 months, respectively. The CRT of the eyes treated with IVB monotherapy, and IVB followed by LP, was significantly reduced (P = 0.012 and P = 0.020, respectively) (Figure 2), whereas the CRT in the nontreatment group had a reduced tendency at 24 months compared with baseline (P = 0.055).
Change in Cystoid Macular Edema
In the treatment group, CME was reduced in 24 eyes (LP alone, 5 eyes; IVB with LP, 10 eyes; IVB alone, 9 eyes) and disappeared in 15 eyes (LP alone, 7 eyes; IVB with LP, 4 eyes; IVB alone, 4 eyes). In the nontreatment group, although CME was reduced in three eyes and maintained in nine eyes, these eyes maintained good visual acuity (VA).
Number of Intravitreal Bevacizumab Administrations
The mean number of IVB administrations in all 22 patients was 2.0 ± 1.5. Of the 22 eyes treated with IVB, in the LP with IVB group, bevacizumab was administered 1.8 ± 1.7 times, and in IVB alone group, 2.1 ± 1.0 times. There were no significant differences in the number of IVB administrations about age, BCVA, and CRT at baseline.
Retinal Vascular Events During the Follow-up Period
Retinal vascular events occurred in seven eyes during the 2-year observational period (14.3%). RVO occurred in six eyes, and retinal macroaneurysm was present in one eye. The onset time of retinal vascular events varied from 7 months to 24 months (21.3 ± 4.9 months) after baseline. RVO occurred in 6 patients (one man and five women) with a mean age of 72.8 ± 9.6 years, mean logMAR BCVA at baseline of 0.28 ± 0.10 (median, 20/36), and mean CRT at baseline of 427.7 ± 141.0 μm. Three of these patients were treated with IVB followed by LP, two with LP alone, whereas the other patient received no treatment.
Medical histories comprised blood hypertension in one patient, blood hypertension and cerebral infarction and myocardial infarction in the second, and both hypertension and cerebral infarction in the third patient. The first and second patients were treated with LP, and the third patient was treated with IVB followed by LP. The fourth patient, who received no treatment, had hypertension, cerebral infarction, and hyperlipidemia. In the remaining three patients (one of them was the patient with MA), there were no medical histories of IVB treatment followed by LP.
The case complicated with retinal macroaneurysm involved a 68-year-old man treated with IVB followed by LP. This patient's logMAR BCVA and CRT were 20/100 and 600 μm at baseline, respectively.
Longitudinal analysis showed that sex, logMAR BCVA at baseline, cerebral infarction, and myocardial infarction were not correlated with any of the retinal vascular events. Only CRT at baseline was significantly correlated with retinal vascular events of Type 1 IMT (P = 0.048, Table 3).
The adverse event of RVO was not correlated with blood hypertension, myocardial infarction, or hyperlipidemia. The risk factors of RVO development were statistically significantly related to sex (P = 0.035) and medical history of brain infarction (P = 0.031). The number of IVB and LP administrations was not related to any of the factors.
A 68-year-old man with Type 1 IMT in his right eye
This patient was treated with LP alone in his right eye (Figure 3). His BCVA was 20/100, and CRT was 600 μm at baseline. Cystoid macula edema decreased gradually after LP treatment. The BCVA improved to 20/40 and CRT reduced to 292 μm at 24 months.
A 72-Year-Old Woman With Type 1 Idiopathic Macula Telangiectasia in Her Right Eye
This case was complicated with branch retina vein occlusion in the patient's right eye during the treatment of Type 1 IMT (Figure 4). The patient was treated with IVB followed by LP. At baseline, BCVA was 20/50 and CRT was 543 μm. After LP treatment followed by two IVB injections, BCVA stabilized, and macular edema disappeared. At 24 months, branch retina vein occlusion occurred in the right eye.
An 82-Year-Old Man With Type 1 Idiopathic Macula Telangiectasia in His Left Eye
This patient was followed up without receiving treatment in his left eye (Figure 5). At baseline, his BCVA was 20/25 and CRT was 331 μm. Because his BCVA was better than 20/33, and his CRT was lower than 350 μm, the eye was not treated, and the natural course was observed over 2 years. Microaneurysm color changed from reddish (arrow in Figure 5A) at baseline to whitish (arrow in Figure 5B) at 24 months. Twenty-four months after baseline, his BCVA was maintained at 20/25, and CRT was reduced to 302 μm.
In this study, we retrospectively evaluated the clinical features of treated and untreated Type 1 IMT eyes followed up for 2 years. There are no established treatments for Type 1 IMT and therapeutic possibilities are limited, although some patients respond to LP.5–7 Only a few cases in which intravitreal triamcinolone was successfully used to treat macular edema related to Type 1 IMT have been reported.9,10 Recently, several studies reporting the use of bevacizumab in the treatment of Type 1 IMT have been published; however, outcomes have been inconsistent.4,12–16 Gamulescu et al8 reported that a single IVB injection markedly increased VA in a Type 1 IMT patient, suggesting that anti-VEGF therapy may be effective at treating the associated visual deterioration. In other reports, the effect of bevacizumab seems to be limited in Type 1 IMT patients compared with Type 2 IMT patients.17 VEGF treatment for Type 1 IMT is therefore controversial.
The reason for the discrepancies in the results of anti-VEGF therapy may be due to differences in treatment protocol. Takayama et al4 reported a treatment protocol for Type 1 IMT as follows: if macular edema did not reduce, additional treatments were performed one to two times at the discretion of the physician at 4-week intervals after treatment. In contrast, Koay et al administered a monthly injection of IVB three times from baseline.13 It is unknown whether VEGF has a function in the pathogenesis of Type 1 IMT. Vascular endothelial growth factor plays an integral part in the formation of abnormal blood vessels and in increasing vascular permeability in many pathologic conditions.17–19 This suggests that late anti-VEGF therapy for long-lasting macular edema or/and edema recurrence produces good anatomical outcomes but does not improve vision. Because these conditions may lead to irreversible retinal damage, early treatment can have a beneficial effect on VA.
In this study, we evaluated the long-term treatment of Type 1 IMT with LP and/or IVB. Laser photocoagulation and/or IVB may be effective at treating macular edema. In the treatment group, BCVA improved in 5 cases and was maintained in 24 cases from baseline to 24 months. In one case treated with IVB monotherapy, this was not accompanied with an increase in VA. When LP is administered alone, if the MA or ectatic parafoveal capillary vessels are too close to the fovea, the following combined IVB therapy must be effective. Although, LP is effective at treating macula edema, recurrence can sometimes occur due to the reopening of capillary vessels or the occurrence of new ectatic capillaries. Furthermore, repetition of LP may lead to parafoveal retinal scarring. Combination therapy with IVB reduces the number of required LP applications.
Some self-limiting eyes maintained good VA in this study, although there are no reports on the natural course of Type 1 IMT. This may be the indication for treatment, which was cases with Snellen BCVA of 20/33 or less, or CRT of at least 350 μm at the initial visit. In fact, in 18 untreated eyes with Type 1 IMT, the mean VA was maintained and the mean CRT reduced significantly between baseline and 24 months. Watzke et al concluded that vision loss was associated with an increase in the extent of Type 1 IMT and intraretinal edema to the point of cyst formation.20 It is important that the VA is improved, and CME slightly improved compared with that at baseline.
Retinal vascular adverse events were observed in seven eyes (14.3%) with Type 1 IMT over the 2-year follow-up period. These retinal events were significantly associated with CRT at baseline. The mechanism of Type 1 IMT pathogenesis appeared to be correlated with other retinal vascular events. Actually, the risk factors of RVO development were statistically significantly related to sex (women) and medical history of cerebral infarction, whereas the number of IVB administrations and LP was not related to any factor. Therefore, during the follow-up period for Type 1 IMT, patient sex and medical history of cerebral infarction must be taken into consideration for the development of other retinal complications, especially RVO.
In conclusion, LP and/or IVB may be effective at treating Type 1 IMT, although treatment was not required over a 2-year follow-up in some cases (36.7%). Furthermore, regardless of the presence or absence of systemic disease, other retinal vascular events were not uncommon in Type 1 IMT. Because this study was retrospective and of a small size, further studies are necessary to confirm findings and to further clarify the clinical significance of visual prognosis in patients with Type 1 IMT.
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Keywords:© 2018 by Ophthalmic Communications Society, Inc.
Type 1 idiopathic macular telangiectasia; macular edema; intravitreal anti-vascular endothelial growth factor; intravitreal bevacizumab; laser photocoagulation; retinal vein occlusion; retinal macroaneurysm; vascular permeability