Outer Retinal Tubulation
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Outer retinal tubulation (ORT) is a feature of photoreceptor rearrangement after retinal injury. Degenerating photoreceptors are arranged in a circular or tubular fashion. ORT is most commonly seen in neovascular age-related macular degeneration (AMD) but is also seen in various chronic degenerative retinal disorders. This process is not disease specific but a general response to various outer retinal degenerative diseases, such as, non-exudative and exudative age-related macular degeneration, retinal dystrophies, choroidemia. It is important to recognize this entity since the ovoid cystic lesions can be misinterpreted to be intraretinal fluid prompting initiation of unnecessary treatment.
With spectral-domain optical coherence tomography (OCT), ORT has the distinctive feature of round or ovoid hyporeflective spaces with hyperreflective borders located at the outer nuclear layer (Figure 1). En face OCT shows that ORT has a branching network.
The adaptive optics scanning laser ophthalmoscope (AOSLO) imaging shows ORTs as hyporeflective areas that ranging in length from small tubes to extending as long as the width of atrophy.
In a retrospective study of 238 eyes of 119 patients, geographic atrophy and subretinal hyperreflective material were baseline risk factors for development of ORT.
The exact pathogenesis is unknown. It is postulated that after retinal injury, degenerating photoreceptors lose adhesions to surrounding structures; the remaining viable photoreceptors reorganize by inward folding of the photoreceptor layer with external limiting membrane to attain new lateral contact between photoreceptors to form tubular structure.It is postulated that this tubular arrangement may be provide some survival benefit for the photoreceptors located over diseased or atrophic retinal pigmented epithelium.
Recently the evolution of ORT has been described in 4 phases as nascent, mature, degenerate, and end stage depending on the contents within the tubule walls. The SD-OCT showed changes in the ELM in areas adjacent to geographic atrophy.
Histological and transmission electron microscopy suggest the hyperreflective border of ORT consists of external limiting membrane and photoreceptor inner segment mitochondria. As nicely stated by Dolz-Marco, "The main histologic characteristics of ORT include: (1) location at the level of the outer nuclear layer, (2) presence of an ELM delimiting all or part of the lumen, (3) presence of surrounding radially oriented photoreceptors pointing into the lumen, and (4) degeneration or absence of the underlying RPE. ORTs are commonly found at the border of relatively normal and atrophic outer retina. These can change but may remain relatively stable over a period of time.
ORT has been seen in a variety of retinal disorders:
- Neovascular AMD
- Pseudoxanthoma elasticum with angioid streak
- Choroidal neovascularization secondary to multifocal choroiditis and panuveitis
- Advanced AMD with geographic atrophy
- Chronic central serous chorioretinopathy
- Bietti crystalline dystrophy
- Pattern dystrophy
- Acute zonal occult outer retinopathy
- Retinitis pigmentosa
- Stargardt disease
- Gyrate atrophy
- Best disease
- Diabetic macular edema
- Chronic retinal detachment
The incidence of ORT increases with time in neovascular AMD. One study showed that ORT developed in 17%, 28%, 35% and 41% of eyes after 1, 2, 3 and 4 years of follow up. Another study showed that ORT occurred in 7%, 18% and 31% of eyes after 1, 2 and 3 years, respectively, of follow up.
In neovascular AMD treated with anti-VEGF injections, eyes with ORTs had worse visual acuity, central macular thickness and retinal sensitivity than those without ORT. In addition, eyes with ORT had a slower rate of enlargement of geographic atrophy than those without ORT.
The major differential diagnoses are: cystoid macular edema, intraretinal fluid and subretinal fluid. In contrast to cystoid macular edema, ORT has a distinctive hyperreflective border and is located within the outer retina.
ORT generally remains stable over time. No treatment is required. It is important to recognize ORT and differentiate it from cystoid macular edema, intraretinal or subretinal fluid to avoid unnecessary treatments (Figure 1).
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