Retinitis pigmentosa is a heterogeneous group of diseases that have many causes and different biology, sharing symptoms that may be common and result in deterioration of vision. It is a complicated disease with dominant, recessive, and X-linked forms of inheritance in addition to rare mitochondrial and digenic forms.1,2 It primarily affects the rod and cone photoreceptors and the retinal pigment epithelium.3 Primary retinitis pigmentosa is defined by progressive night blindness, electroretinographic decline, constriction and gradual loss of the visual field, and loss of visual acuity.3 The loss of visual acuity can vary from mild to profound no light perception.4,5 Cystoid macular edema and rod and cone photoreceptors abnormalities leading to retinal thinning at the macula are the main causes of severe visual deterioration in those patients.6 Patients with retinitis pigmentosa and cystoid macular edema have been observed because of the medical or surgical therapeutic possibilities.7,8
Optical coherence tomography (OCT) is a well-established method of obtaining in vivo cross-sectional tomographic images of the retina. OCT has proven useful and accurate in measuring retinal thickness in various diseases.9–13 Several studies of retinitis pigmentosa using OCT demonstrate the capability of OCT to diagnose and follow the cystoid macular edema in a quantitative manner before and after therapeutic intervention in patients with retinitis pigmentosa.14–16
Our study focused on patients with retinitis pigmentosa who had a visual acuity of 20/200 or worse and used OCT to identify specific characteristics related to the thickness and morphology of the retina in the macular region.
Patients and Methods
We collected the files of all patients who were diagnosed as having retinitis pigmentosa and presented to the 2nd Ophthalmology Department of Henry Dunant Hospital between March 2003 and January 2007. We also reviewed the files of all patients with retinitis pigmentosa who presented individually to the Henry Dunant and Attikon Hospitals. One hundred eighteen patients with retinitis pigmentosa were identified based on a history of night blindness, characteristic pigmentary changes of the retina, and reduction in electroretinogram rod and cone amplitudes.
Inclusion criteria for the current study were the diagnosis of retinitis pigmentosa and a visual acuity of 20/200 or worse. Twenty-five patients met the inclusion criteria. However, in 4 patients it was not possible to identify the fovea by OCT. Therefore, 42 eyes of 21 patients were included in this retrospective observational case series. The patients had no other ocular diseases except epiretinal membrane, which often accompanies retinitis pigmentosa, nor were they taking medications that could affect retinal function.
The study was conducted according to the tenets of the Declaration of Helsinki and all participants gave informed consent after the purpose of the study had been explained to them. The Ethics Committee of Henry Dunant Hospital approved the study.
All patients had a complete clinical examination including best-corrected Snellen visual acuity, slit-lamp biomicroscopy, indirect ophthalmoscopy, fundus photography, fluorescein angiography, and OCT examination. Visual acuity was measured using the Snellen chart for acuities as low as 20/400. For visual acuities lower than 20/400 and hand motions, we used the conversion chart provided by Schulze-Bonsel et al.17
OCT was performed by OCT3 (Zeiss Stratus OCT Model 3000; Carl Zeiss Meditec, Dublin, CA). Six 6-mm radial scans centered on the fovea were performed by an experienced examiner at angles separated from each other by 30° intervals to create a map of the macula. Horizontal and vertical linear scans of variable length were also performed over the macular area to provide a detailed examination of the retina. Because of the poor fixation of many patients due to low visual acuity, a large number of horizontal and vertical linear scans were obtained by scanning the whole macular area extending between the vascular arcades vertically, the optic disc nasally, and as far as 2 optic disc diameters temporally in the horizontal direction. We used the normal scan protocols provided by the OCT software for improved resolution and not the fast scan protocols.
In the cases where the fixation was adequate, the OCT software automatically calculated the retinal thickness of the foveola and the surrounding retina. In the patients with poor fixation, the foveola was identified manually and the retinal thickness was automatically measured by the OCT software. Where this was not possible due to errors induced by faulty computer algorithm identification of the inner and outer retina, the retinal thickness of the foveola was measured manually using the electronic caliper of the OCT software perpendicular to the retinal pigment epithelium–photoreceptors interface, which has been used in cases of choroidal neovascular membrane due to age-related macular degeneration.18
Forty-two eyes of 21 patients were included in the study. Eight (38.1%) patients were women and 13 (61.9%) were men. The mean ± standard deviation (SD) age was 44.5 ± 13.3 years (median: 42 years; range: 14 to 73 years). Mean visual acuity was 20/660, (median: counting fingers; range: 20/200 to hand motions). The refraction of all patients ranged from −6.00 to +3.00 diopters spherical equivalent (mean: −2.00 ± 3.1 diopters; median: −1.75 diopters). Twenty-two (52.4%) eyes had clear crystalline lens, 14 (33.3%) had undergone cataract extraction with intraocular lens insertion, and 6 (14.3%) had a mild cataract that did not preclude the reliable examination of the retina.
OCT examination of the fovea revealed an atrophic retina (group 1) in 34 (81%) eyes (Fig. 1) and 8 (19%) eyes with cystoid macular edema (group 2) (Fig. 2). The mean ± SD thickness of the retina at the foveola was 113.9 ± 73.75 μm. The mean ± SD retinal thickness at the foveola was 87.7 ± 44.6 μm (range: 0 to 183 μm) in eyes with an atrophic retina and 229.9 ± 65.9 μm (range: 140 to 318 μm) in eyes with cystoid macular edema. The mean visual acuity of the eyes with an atrophic retina was 20/1000 compared to a better mean visual acuity of 20/300 for the eyes with cystoid macular edema, reaching marginal statistical significance (P = .042, Wilcoxon signed rank test).
Figure 1. Patient with Retinitis Pigmentosa and Atrophic Retina. The Retinal Thickness at the Foveola Is 41 μm. Note the Absence of Most Retinal Layers.
Figure 2. Patient with Retinitis Pigmentosa and Cystoid Macular Edema at the Fovea. The Retinal Thickness at the Foveola Is 255 μm. Note the Large Hyporeflective Cystic Spaces at the Foveola.
In eyes with an atrophic retina, a degree of disintegration was noted at the macula. The retina appeared thin in the area surrounding the foveola, reaching the total absence of retinal tissue at the foveola in some cases. In the eyes with cystoid macular edema, there was also retinal disintegration with disruption of the retinal pigment epithelium and intraretinal cystoid spaces of low reflectivity. In both groups, the line indicating the junction between the inner and outer segments of the photoreceptors could not be identified in any case. There were areas of chorioretinal scars at the foveola of many patients in the form of a thick band of high reflectivity underlying the retinal pigment epithelium–choriocapillaries complex and large areas of disrupted retinal pigment epithelium in the macular area of most patients.
Epiretinal membrane was identified in 27 (64.3%) eyes. Nineteen (55.9%) eyes with atrophic retina had epiretinal membrane compared to 8 (100%) eyes with cystoid macular edema. In 8 (19%) of the 42 eyes, the vitreous was found to be attached to the fovea on OCT examination; 6 (75%) of those had atrophic retina at the foveola and the remaining 2 (25%) had cystoid macular edema. Of the 14 pseudophakic eyes, 13 had atrophic retina and 1 had cystoid macular edema. Fluorescein angiography was able to detect macular edema in 3 patients with cystic OCT appearance of the fovea. In the rest of the patients, fluorescein angiography did not show any leakage at the macula even at the late phases. Ophthalmoscopic examination of the macula did not reveal cystoid macular edema in any of the patients. In the cases with atrophic retina, fluorescein angiography showed hyperfluorescence due to window defect without active leakage.
The retina and the photoreceptors layer of the macular area in rds/rds mice and rd/rd/+ transgenic mice with photoreceptor degeneration have shown progressive thinning when examined by OCT.19,20 Patients with retinitis pigmentosa and allied diseases have also been studied by OCT to demonstrate the retinal degenerative changes that occur in those eyes.21,22 The presence of cystoid macular edema in patients with retinitis pigmentosa has been described previously as one of the main causes of visual acuity deterioration.7,8,14,16,23,24 However, to our knowledge, there is no previous report on the use of OCT in patients with retinitis pigmentosa and a visual acuity 20/200 or less.
In our study of patients with retinitis pigmentosa and low visual acuity, we found that the main characteristic was the atrophic retina at the fovea (81%), with only a small group of patients (19%) with cystoid macular edema. In group 1, the foveal thickness was significantly lower than in group 2 (87.7 ± 44.6 μm compared to 229.9 ± 65.9 μm). Patients with atrophic retina (mean: 20/1000) had worse visual acuity compared to those with cystoid macular edema (mean: 20/300), which is to be expected with such a degree of marked retinal atrophy at the foveola.
Patients with atrophic retina had absence of the photoreceptors layer and a marked thinning of the retina. In the 1-mm diameter area of the fovea, there was chorioretinal scarring with thinning of the surrounding retina. Patients with cystoid macular edema had disrupted retinal pigment epithelium and photoreceptors at the foveola, with some cases having diffuse thickening of the retina at the foveola with few empty cystic spaces within. In all eyes, the photoreceptors layer could not be identified.
This is in agreement with Witkin et al.,25 who observed the disappearance of the highly reflective band of the photoreceptors and a reduction in the thickness of the “foveal outer segment/pigment epithelium” zone in eyes with retinitis pigmentosa and reduced visual acuity compared to the healthy individuals. Sandberg et al.26 categorized patients with retinitis pigmentosa as having the highly reflective band of the photoreceptors absent, partially distinct, or intact and they found that visual acuity declined significantly with declining band definition. They also found that visual acuity was most strongly related to retinal thickness in eyes with an absent highly reflective band of the photoreceptors and was not related to retinal thickness in eyes with an intact band.
This is in agreement with our results in which no patient had the highly reflective band of the photoreceptors and all eyes had a visual acuity of 20/200 or worse. We also observed that the visual acuity in eyes with cystoid macular edema was better compared to the patients with atrophic retina, giving support to Sandberg et al.’s observations.26
Of the 8 eyes with cystoid macular edema, only 1 was pseudophakic. Because this represents a rate of only 7.1% in the 14 pseudophakic eyes, we believe the cystoid macular edema is unlikely to be due to the cataract operation rather than the disease itself.
Fluorescein angiography was able to detect macular edema in only 3 patients with cystoid macular edema. In the rest of the patients in this group, fluorescein angiography did not show any leakage at the macula even at the late phases. In the eyes with atrophic retina, fluorescein angiography showed hyperfluorescence due to window defect without active leakage. Previous reports have shown the limitation of fluorescein angiography in detecting dye leakage in the macula of patients with retinitis pigmentosa, making OCT a more sensitive method for macular edema detection in retinitis pigmentosa.14,16,23 Therefore, patients with retinitis pigmentosa and OCT-diagnosed macular edema have improved chances to receive treatment, which may lead to reduction of the edema and improvement in visual acuity.7,8,14,23,24,27
Epiretinal membrane was identified in 27 (64.3%) eyes. Nineteen (55.9%) eyes with atrophic retina had epiretinal membrane compared to 8 (100%) eyes with macular edema. The epiretinal membrane was more prominent in the eyes with macular edema compared to the subtle appearance of the epiretinal membrane in the eyes with atrophic retina.
OCT examination of those patients was challenging due to the low visual acuity of most and their inability to fixate. Apart from the 6 radial scans centered on the fovea to create a map of the macula, horizontal and vertical linear scans of variable length were also performed over the macula area to provide a detailed examination of the retina. Because of the poor fixation of many patients due to the low visual acuity, we excluded cases where the fovea could not be identified by OCT.
Numerous horizontal and vertical linear scans were obtained by scanning the whole macular area, extending between the vascular arcades vertically, the optic disc nasally, and as far as 2 optic disc diameters temporally in the horizontal direction. Then, in cases where the fixation was adequate, the OCT software automatically calculated the retinal thickness of the foveola and the surrounding retina. In the patients with poor fixation, the foveola was identified manually and the retinal thickness was automatically measured by the OCT software. Where this was not possible due to errors induced by faulty computer algorithm identification of the inner and outer retina, the retinal thickness of the foveola was measured manually using the electronic caliper of the OCT software.18,28 The center of the fovea was included in our calculations. Because the photoreceptors layer could not be identified in any case, all OCT calculations, whether done automatically by the OCT software or manually using the electronic caliper, measured the correct retinal thickness in all patients.
There are several limitations to this study, including the small patient number, the use of Snellen eye charts to measure visual acuity, and the inability of some patients to fixate on the OCT target. We are also aware that ultra-high resolution OCT is able to better identify the retinal layers in patients with retinitis pigmentosa and good visual acuity, but in cases with retinitis pigmentosa and low visual acuity the absence of the photoreceptors layer is evident by both OCT3 and ultra-high resolution OCT.25 Nevertheless, our study has shown that 81% of patients with retinitis pigmentosa and visual acuities of 20/200 or less have atrophic retina at the fovea, whereas the remaining 19% of eyes develop macular edema. OCT is a more sensitive method in detecting macular edema in patients with retinitis pigmentosa than fluorescein angiography and can be helpful in selecting the eyes with retinitis pigmentosa that are amenable to treatment.
The OCT study of patients with retinitis pigmentosa and low visual acuity gives us a representative description of the macular status of those eyes, allowing us to decide if and when it is appropriate to apply a treatment modality.
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- Milam AH, Li ZY, Fariss RN. Histopathology of the human retina in retinitis pigmentosa. Prog Retin Eye Res. 1998;17:175–205.
- Garcia-Arumi J, Martinez V, Sararols L, Corcostegui B. Vitreoretinal surgery for cystoid macular edema associated with retinitis pigmentosa. Ophthalmology. 2003;110:1164–1169. doi:10.1016/S0161-6420(03)00259-8 [CrossRef]
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- Hee MR, Puliafito CA, Wong C, et al. Optical coherence tomography of macular holes. Ophthalmology. 1995;102:748–756.
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- Hee MR, Baumal CR, Puliafito CA, et al. Optical coherence tomography of age-related macular degeneration and choroidal neovascularization. Ophthalmology. 1996;103:1260–1270.
- Hee MR, Puliafito CA, Duker JS, et al. Topography of diabetic macular edema with optical coherence tomography. Ophthalmology. 1998;105:360–370. doi:10.1016/S0161-6420(98)93601-6 [CrossRef]
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- Hirakawa H, Iijima H, Gohdo T, Tsukahara S. Optical coherence tomography of cystoid macular edema associated with retinitis pigmentosa. Am J Ophthalmol. 1999;128:185–191. doi:10.1016/S0002-9394(99)00100-2 [CrossRef]
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