Idiopathic juxtafoveolar retinal telangiectasis (IJRT),1,2 or idiopathic macular telangiectasia (IMT),2 refers to a heterogeneous group of well-recognized clinical entities characterized by telangiectatic alterations of the juxtafoveolar capillary network of 1 or both eyes. Classically, 3 groups of IJRT are identified.3 These groups differ in appearance, presumed pathogenesis, and management strategies. Group 1 is unilaterally easily visible telangiectasis occurring predominantly in men and causes visual loss as a result of macular edema. Group 2, the most common, is bilateral occurring in both middle-aged men and women, and presents with telangiectasis that is more difficult to detect on biomicroscopy in early stages, but that has characteristic and diagnostic angiographic and optical coherence tomography (OCT) features. Group 2 is divided into 2A, acquired, and 2B, congenital. Yannuzzi et al2 subdivided type 2A into nonproliferative (telangiectasis, exudation, intraretinal pigments, and foveal atrophy) and proliferative disease (subretinal neovascularization [SRNV] or fibrosis). Vision loss in group 2 is due to retinal atrophy, not exudation, and subretinal neovascularization.4 Group 3 is very rare and characterized predominantly by bilateral progressive obliteration of the perifoveal capillary network without exudation, and usually occurs in association with a medical or neurologic disease.5

Type 2A IJRT

IJRT type 2A is the most common type of IJRT in our clinic. The precise pathogenesis of IJRT type 2A is controversial. Primary degeneration or dysfunction of the parafoveolar Mueller cells leads to retinal thinning, particularly photoreceptor atrophy and retinal endothelial cell dysfunction. Photoreceptor atrophy leads to invasion of proliferating capillaries into subretinal space, causing SRNV and later anastomosis with the choroidal vessels.6 A recent report from Kurihara et al7 reported blocking VEGF-A in adult mouse retinal pigment epithelial (RPE) cells rapidly led to vision loss and ablation of the choriocapillaris.

Fluorescein angiography in IJRT type 2A will typically reveal parafoveal ectatic capillaries and late-stage diffuse leakage, mainly temporal to the fovea. Both atrophy and secondary choroidal neovascularization have been reported to occur with disease progression.8 Imaging with OCT typically shows intraretinal hyporeflective spaces in the foveal region, thinning and disruption of the photoreceptor layer; and intraretinal hyperreflective lesions causing posterior shadowing corresponding to hyperpigmented RPE plaques. In the presence of SRNV, highly reflective dots in the inner and outer nuclear layers with intraretinal/subretinal fluid with or without localized increase in retinal thickness are noted.9,10 Change in autofluorescence can be helpful in early diagnosis and to follow the progression of disease. Disruption of foveal autofluorescence, hypoautofluorescence corresponding to pigments, and hypo- or hyperautofluorescence in parafoveal areas are common changes in fundus autofluorescence.11

In their histological analysis, Green et al12 described thickening of the wall of retinal capillaries resulting from proliferation of basement membrane and narrowing of the capillary lumen in an eye with type 2 IJRT. They also observed degeneration of pericytes and occasional areas of degenerated endothelial cells.

Anti-VEGF Therapy for SRNV in Type 2A IJRT

Intravitreal inhibition of VEGF has been shown to be effective for a variety of ocular diseases with destabilized blood-retina barrier or pathologic growth of new vessels. 13-16 Recently, it has been hypothesized that VEGF may play an essential role in the pathogenesis of macular telangiectasia as well.17,18 Charbel Issa et al17 showed a reduction in the ectatic capillaries in early stage on fluorescein angiography as well as marked reduction in size and intensity of late stage hyperfluorescence at 4 and 8 weeks after injection of anti-VEGF agents in eyes with IJRT. This reduction in leakage suggests the role of VEGF in extravasation of fluorescein through altered endothelium. OCT imaging revealed decrease in intraretinal thickness as well. However, this effect was temporary, and rebound increase in parafoveal leakage and central retinal thickness was noted.18 Similarly, several studies reported decrease in leakage in nonproliferative IJRT with intravitreal bevacizumab.19-22

Charbel Issa et al17 hypothesized that these structural capillary changes could lead to a disturbed exchange of oxygen and substrates between the vascular lumen and neurosensory retina. This may lead to a hypoxia-induced increased VEGF release by retinal cells. The loss of pericytes may render the capillaries more susceptible to effects mediated by VEGF.

In previous studies, however, there were no shortterm visual acuity or anatomic improvements in nonproliferative IMT eyes after intravitreal anti-VEGF treatment, which suggests that there may be no short-term benefit in treating before the development of SRNV. Takayama et al23 also showed no effect of intravitreal bevacizumab on retinal thickness or intraretinal cysts in type 1 IJRT. VEGF is thought to play a role in vitro photoreceptor survival.6 Anti-VEGF agents may cause photoreceptor degeneration. Therefore, use of anti-VEGF drugs in the nonproliferative stage is still controversial.

Other Therapies for SRNV in Type 2A IJRT

SRNV in type 2A IJRT is unique in its origin. Yannuzzi et al24 termed this intraretinal SRNV as type 3 neovascularization, similar to early retinal angiomatous proliferation, and different from type 1 (under the retinal pigment epithelium or occult) and type 2 (above pigment epithelium or classic) neovascularizations, which originate from the choroid in age-related macular degeneration.

SRNV is the only treatable cause of vision loss in eyes with type 2A IJRT. The SRNV lesions are not usually large; they begin in the retina and then progress into the subretinal space. Numerous treatments have been tried, including focal/grid laser,25 surgical removal of the subretinal neovascular membrane,26 transpupillary thermotherapy,27 photodynamic therapy (PDT),28,29 and intravitreal triamcinolone acetonide.30 These treatment modalities failed to maintain or improve visual acuity.25,26,31 PDT may lead to RPE atrophy after treatment with no visual improvement and associated with higher incidence of recurrence and excessive scarring.31 Surgical removal of the SRNV is difficult because of strong adhesion with the overlying neurosensory retina. 26 Intravitreal triamcinolone is generally associated with cataract progression and glaucoma.

Although the etiology of type 2A IJRT is not clearly understood, VEGF seems to have a role in the pathogenesis of SRNV. Several case reports and our case series reported the resolution of subretinal and intraretinal fluid on OCT and the regression of SRNV with cessation of SRNV leakage along with significant improvement in visual acuity in eyes treated with intravitreal anti-VEGF monotherapy (Figure 1).19,32,33 Mean number of injections in our study was 1.9 (range, 1-3). Improvement in visual acuity and control of SRNV with anti-VEGF drugs makes this the preferred treatment. In our series, we found that ranibizumab and bevacizumab were both equally effective, although there were insufficient data in the study to conclusively prove this.

Summary

The role of anti-VEGF drugs in visual acuity or structural improvement in nonproliferative type 2A IJRT is still controversial. Anti-VEGF drugs definitely help to prevent disease progression and maintain or improve visual acuity in eyes with SRNV associated with type 2A IJRT. Larger series with long-term follow-up, however, are needed to address the long-term outcomes, the needed frequency of anti-VEGF administration, and its side effects.

Jay Chhablani, MD, is a Vitreoretinal Consultant at L.V.Prasad Eye Institute, Kallam Anji Reddy Campus in Banjara Hills, Hyderabad, India. Dr. Chhablani states that he has no financial interests or relationships to disclose. He may be reached at jay.chhablani@gmail.com.

Nishant Radke, MD, is a Vitreoretinal Consultant at Vasan Eye Care Hospitals in Nasik, India. Dr. Radke states that he has no financial interests or relationships to disclose.

Igor Kozak, MD, is a Vitreoretinal Consultant at King Khaled Eye Specialist Hospital in Riyadh, Kingdom of Saudi Arabia. Dr. Kozak states that he has no financial interests or relationships to disclose.

  1. Gass JD, Oyakawa RT. Idiopathic juxtafoveolar retinal telangiectasis. Arch Ophthalmol. 1982;100:769-780.
  2. Yannuzzi LA, Bardal AM, Freund KB, Chen KJ, Eandi CM, Blodi B. Idiopathic macular telangiectasia. Arch Ophthalmol. 2006;124:450-460.
  3. Gass JD, Blodi BA. Idiopathic juxtafoveolar retinal telangiectasis. Update of classification and follow-up study. Ophthalmology. 1993;100:1536-1546.
  4. Shukla D, Gupta SR, Neelakantan N, et al. Type 2 idiopathic macular telangiectasia. Retina. 2012;32:265-274.
  5. Nowilaty SR, Al-Shamsi HN, Al-Khars W. Idiopathic juxtafoveolar retinal telangiectasis: a current review. Middle East Afr J Ophthalmol. 2010;17:224-241.
  6. Yourey PA, Gohari S, Su JL, Alderson RF. Vascular endothelial cell growth factors promote the in vitro development of rat photoreceptor cells. J Neurosci. 2000;20:6781-6788.
  7. Kurihara T, Westenskow PD, Bravo S, Aguilar E, Friedlander M. Targeted deletion of Vegfa in adult mice induces vision loss. J Clin Invest. 2012;122:4213-4217.
  8. Narayanan R, Majji AB, Hussain N, et al. Characterization of idiopathic macular telangiectasia type 2 by fundus fluorescein angiography in Indian population. Eur J Ophthalmol. 2008;18:587-590.
  9. Gaudric A, Ducos de Lahitte G, Cohen SY, Massin P, Haouchine B. Optical coherence tomography in group 2A idiopathic juxtafoveolar retinal telangiectasis. Arch Ophthalmol. 2006;124:1410-1419.
  10. Paunescu LA, Ko TH, Duker JS, et al. Idiopathic juxtafoveal retinal telangiectasis: new findings by ultrahighresolution optical coherence tomography. Ophthalmology. 2006;113:48-57.
  11. Chhablani JK, Narayanan R. Fundus autofluorescence patterns in type 2A idiopathic juxtafoveolar retinal telangiectasis. Eur J Ophthalmol. 2012;22:398-403.
  12. Green WR, Quigley HA, De la Cruz Z, Cohen B. Parafoveal retinal telangiectasis. Light and electron microscopy studies. Trans Ophthalmol Soc U K. 1980;100:162-170.
  13. Avery RL. Regression of retinal and iris neovascularization after intravitreal bevacizumab (Avastin) treatment. Retina. 2006;26:352-354.
  14. Avery RL, Pearlman J, Pieramici DJ, et al. Intravitreal bevacizumab (Avastin) in the treatment of proliferative diabetic retinopathy. Ophthalmology. 2006;113:1695, e1691-1615.
  15. Avery RL, Pieramici DJ, Rabena MD, Castellarin AA, Nasir MA, Giust MJ. Intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration. Ophthalmology. 2006;113:363-372, e365.
  16. Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 2006;355:1419-1431.
  17. Charbel Issa P, Holz FG, Scholl HP. Findings in fluorescein angiography and optical coherence tomography after intravitreal bevacizumab in type 2 idiopathic macular telangiectasia. Ophthalmology. 2007;114:1736-1742.
  18. Matsumoto Y, Yuzawa M. Intravitreal bevacizumab therapy for idiopathic macular telangiectasia. Jpn J Ophthalmol. 2010;54:320-324.
  19. Kovach JL, Rosenfeld PJ. Bevacizumab (Avastin) therapy for idiopathic macular telangiectasia type II. Retina. 2009;29:27-32.
  20. Lira RP, Silva VB, Cavalcanti TM, de Souza AC, Pinto AP. Intravitreous ranibizumab as treatment for macular telangiectasia type 2. Arch Ophthalmol. 2010;128:1075-1078.
  21. Charbel Issa P, Finger RP, Holz FG, Scholl HP. Eighteen-month follow-up of intravitreal bevacizumab in type 2 idiopathic macular telangiectasia. Br J Ophthalmol. 2008;92:941-945.
  22. Charbel Issa P, Finger RP, Kruse K, Baumuller S, Scholl HP, Holz FG. Monthly ranibizumab for nonproliferative macular telangiectasia type 2: a 12-month prospective study. Am J Ophthalmol. 2011;151:876-886, e871.
  23. Takayama K, Ooto S, Tamura H, et al. Intravitreal bevacizumab for type 1 idiopathic macular telangiectasia. Eye (Lond). 2010;24:1492-1497.
  24. Yannuzzi LA, Freund KB, Takahashi BS. Review of retinal angiomatous proliferation or type 3 neovascularization. Retina. 2008;28:375-384.
  25. Park DW, Schatz H, McDonald HR, Johnson RN. Grid laser photocoagulation for macular edema in bilateral juxtafoveal telangiectasis. Ophthalmology. 1997;104:1838-1846.
  26. Berger AS, McCuen BW 2nd, Brown GC, Brownlow RL Jr. Surgical removal of subfoveal neovascularization in idiopathic juxtafoveolar retinal telangiectasis. Retina. 1997;17:94-98.
  27. Nachiappan K, Shanmugam MP. Treatment of CNVM secondary to idiopathic juxtafoveal retinal telangiectasis by transpupillary thermotherapy. Am J Ophthalmol. 2005;139:577-578; author reply 578.
  28. Potter MJ, Szabo SM, Chan EY, Morris AH. Photodynamic therapy of a subretinal neovascular membrane in type 2A idiopathic juxtafoveolar retinal telangiectasis. Am J Ophthalmol. 2002;133:149-151.
  29. Snyers B, Verougstraete C, Postelmans L, Leys A, Hykin P. Photodynamic therapy of subfoveal neovascular membrane in type 2A idiopathic juxtafoveolar retinal telangiectasis. Am J Ophthalmol. 2004;137:812-819.
  30. Alldredge CD, Garretson BR. Intravitreal triamcinolone for the treatment of idiopathic juxtafoveal telangiectasis. Retina. 2003;23:113-116.
  31. Shanmugam MP, Agarwal M. RPE atrophy following photodynamic therapy in type 2A idiopathic parafoveal telangiectasis. Indian J Ophthalmol. 2005;53:61-63.
  32. Mandal S, Venkatesh P, Abbas Z, Vohra R, Garg S. Intravitreal bevacizumab (Avastin) for subretinal neovascularization secondary to type 2A idiopathic juxtafoveal telangiectasia. Graefes Arch Clin Exp Ophthalmol. 2007;245:1825-1829.
  33. Shanmugam MP, Mythri HM, Shetty NS. Intravitreal bevacizumab for parafoveal telangiectasia-associated choroidal neovascular membrane. Indian J Ophthalmol. 2007;55:490-491.