Multimodal Imaging Biomarkers in monitoring the progression of Macular Telangiectasia.

INTRODUCTION: Idiopathic maculartelangiectasia (MacTel) is retinal capillary ectasia, which is limited to theperifoveal area. In 1982 Gass and Oyakawa classified  IJRT(idiopathic juxtafoveal retinal telangiectasia)into four groups based on clinical and fluorescein angiographic findings. In1993 Gass and Blodi modified it-IJRT was subdivided into 3 groups and eachgroup further into two subgroups.  LaterYanuzzi et al simplified Gass classification, correlating with findings in OCT,high speed Indocyanin Green and fluorescein angiography findings:

(1)   aneurysmaltelangiectasia or idiopathic macular telangiectasia type 1 which includes Gass1A and 1B subgroups

(2) perifovealtelangiectasia or idiopathicmacular telangiectasia type 2 which includes Gass 2A sub-group.

Gass 2B and 3 groupswere not included in that due to rarity of diseases. Chew et al classified MacTel2 into non-proliferative (telangiectasia and foveal atrophy) and proliferativewhich shows  subretinal neovascularization(SRNV)1.

YANUZZI  et al classification

Aneurysmal telangiectasia or MacTel 1

Perifoveal

telangiectasia or MacTel 2

  |Gass and Blodi classification

1A

1B

2A

2B

3A

3B

|Visible and exudative

Visible exudative and focal

Occult and non-exudative

Juvenile, occult, familial

occlusive

Occlusive, association with CNS vasculopathy

Most common of theseis MacTel type 2A. Idiopathic macular telangiectasia type 2 is a bilateral diseasethat affects men and women, mostly seen from fifth and sixth decades of life.MacTel type 2 (MacTel 2) is a bilateral disease characterized by changes in thecapillary network and neurosensory atrophy. Slit lamp bio-microscopy revealsreduced retinal transparency, crystalline deposits, ectatic capillaries andblunted venules. Early features of the disease includes loss of transparency, superficialretinal crystalline deposits, right angled venules and presence of intra-retinalcystoid spaces in the fovea. In later stages, the intra-retinal pigment plaquesand sub-retinal neovascular membrane develops. FFA (fundus fluorescein angiography)is considered as the gold standard for the diagnosis of MacTel, shows dilated,blunted right-angled veins, dilated capillaries in the deep retinal plexus,hyperfluorescence in the early and/or late phase. Optical coherence tomography(OCT) shows thinning of macula. In some cases cavitation in the inner retina orouter retina, or both is seen. A minority progress to develop full thicknessmacular holes. Stereoscopic color and red-free fundus photography shows loss ofretinal transparency, inner retinal crystals, and in later disease pigmentplaques in the mid retina. Several studies suggested that muller cellinvolvement is a main feature of MacTel2. OCTA (Optical coherence tomographyangiography) is a newer noninvasive imaging modality which is found to beuseful in MacTel. Progressive changes over time have been described in MacTelusing each of the imaging techniques, but data on the correlation between signsapparent in these imaging modalities are very limited. Also very few studiesare conducted on OCTA findings in MacTel.

This study plans tocompare and correlate findings with symptoms in various imaging modalities like SD-OCT (Spectral Domain-OCT), FAF (FundusAuto Fluorescence), Multi-colour photography and OCTA in MacTel and also tomonitor the progression in these biomarkers over one year period usingmultimodal imaging and to correlate it with vision.

REVIEW OF LITERATURE:

A retrospective reviewstudy conducted by Spaide et al on volume rendered angiographic and structuralOCTA in MacTel-2 used multimodal imaging to evaluate right angle veincomplexes, macular cavitation and deep retinal invasion and observed contractilefeatures of the tissue in the temporal macula. Study states OCTA is useful in MacTel2 to study vascular interrelationship and association with cavitation2.

Luiz Roisman a, b.,Philip J. Rosenfeld studied OCTA imaging in MacTel type 2 and observed OCTA issuperior to other multimodal imaging3.

A cross-sectionalstudy on characteristics and quantification of vascular changes in MacTel type2 was conducted  by Chidambara et al in AsianIndian population, published in British Journal of Ophthalmology,  on 56 eyes of 28 patients  with MacTel2  during a 3 month period  using fundus photography, SD-OCT,OCTA. FFA wasdone in indicated cases only. Mean capillary density was calculated using anautomated software and found out that mean capillary density of the superficialand deep layers was reduced -39.99% and 39.03% in cases as against 45.18% and44.21% in controls respectively. They concluded that OCTA helps to understandthe pathology better4.

A Study by Sallo et al,published in Retina, the journal of retinal and vitreous diseases, whichcompared the different imaging modalities in macular telangiectasia Type 2.Signs in fundus fluorescein angiography, optical coherence tomography anddual-wavelength auto-fluorescence images were analyzed. One hundred andninety-one eyes of 96 patients were studied. Correlations between early and late fundus fluorescein angiography,luteal pigment loss and early/late fundus fluorescein angiography signs, innerand outer segment break length and pigment loss were significant. Fair correlationbetween pigment loss and retinal spaces/atrophic retinal restructuring observed.Bilateral symmetry was slight to substantial5.

Zhang et al conducteda prospective observational study to image sub-retinal neovascularization inproliferative macular telangiectasia type 2 (MacTel2) using swept sourceoptical coherence tomography based micro-angiography (OMAG). Three eyes with neovascularMacTel2 were imaged with OMAG algorithm. It generated en face flow images fromthree layers of retina, as well as from the region bounded by the outer retinaand Bruch’s membrane, the choriocapillaries, and the remaining choroidalvasculature. The OMAG images were then compared to images from fundusfluorescein angiography (FFA) and indocyanine green angiography (ICGA).Theneovascularization was best identified from the en face OMAG images thatincluded a layer between the outer retinal boundary and Bruch’s membrane6.

A Case study was conducted to report the optical coherencetomographic angiography findings and response to treatment in a case of maculartelangiectasia Type 2 with sub-retinal neovascularization by S.R.Sadda, patientwas treated with intravitreal aflibercept, and they observed a remarkablereduction of flow in the sub-retinal neovascular network on optical coherencetomographic angiography7.

Lisa Toto, Luca Di Antonio by meansof optical coherence tomography angiography (OCTA),studied morphologic features of idiopathic macular telangiectasia(MacTel) type 2 and then it was compared to findings of fundus fluoresceinangiography (FFA), fundus auto-fluorescence (FAF), confocal blue reflectance(CBR), and spectral-domain OCT (SD-OCT)8.

AIMSAND OBJECTIVE**:**

AIM:-To study and monitor the progression in biomarkers inpatients diagnosed with macular telangiectasia at GIRIDHAR EYE INSTITUTE, atertiary eye care center in Kerala.

OBJECTIVE:

1.       To assess the biomarkers in retina, inpatients diagnosed with macular telangiectasia

2.      To assess the progression of thedisease using multimodal imaging methods and correlate it with the symptoms ifany and visual acuity.

MATERIALS ANDMETHOD**:**

• Study area: Giridhar Eye Institute , Kochi
• Study population: OPD patients diagnosed with macular telangiectasia
• Inclusion criteria: all patients diagnosed with macular telangiectasia
• Study design: prospective observational study
• Sample size: 50 eyes

FYI:   The sample size wascalculated using the below formula

whereZ1- α/2      =     1.96

p***=***Expected Proportion

d            =    Absolute Precision

The minimum sample size required is approximately50 eyes.

Study duration: 18 months

METHODOLOGY

·        Symptomaticand asymptomatic patients who attend , who are diagnosed with macular telangiectasiahave to be identified.

• To assess details and clinical history in detail.
• Then to do multimodal imaging with FFA as when needed to conform diagnosis, FAF,SD-OCT,MULTICOLOR IMAGING and OCTA
• All the same procedure (except FFA) is repeated at 6 months and  1year.

STATISTICALMETHOD:

• Data obtained from patients were recorded and analyzed using Microsoft Excel
• Results of categorical variables will be reported as counts and percentages
• McNemer’s test and Fishers exact test will be used to find the differences between categorical variables.