Retinal vasoproliferative tumour secondary to retinitis pigmentosa sine pigmento

Abstract

Retinitis pigmentosa can be associated with exudative vasculopathy in rare instances, which can manifest as retinal vasoproliferative tumours. We present the case of a 33-year-old woman previously diagnosed with retinitis pigmentosa sine pigmentosa in both eyes. She was asymptomatic and just came in for a routine follow-up eye examination. Thorough examination of the peripheral retina on the right eye revealed a dome-shaped retinal tumour with a feeder vessel and surrounding exudative changes at the superotemporal periphery, consistent with a secondary retinal vasoproliferative tumour from retinitis pigmentosa. She subsequently underwent focal laser photocoagulation of the tumour which resulted in tumour stabilisation. While exudative vasculopathy is very uncommon in retinitis pigmentosa, ophthalmologists need to be aware of its occurrence in such patients. Vision loss may occur from exudation, haemorrhage, retinal detachment and neovascularisation. A thorough examination of the peripheral retina is warranted in these cases.

Background

Exudative vasculopathy can occur as a complication of retinitis pigmentosa in about 5% of cases.¹ The pathophysiology is unclear, but chronic retinal ischaemia secondary to attenuation of retinal vessels, exudation from incompetent retinal vessels and chronic damage in the retinal pigment epithelium are implicated in the disease process. The manifestations of exudative vasculopathy include choroidal neovascularisation, Coats-like disease and development of vasoproliferative tumours (VPTs).²

We present the diagnosis and management of this rare complication of retinitis pigmentosa, highlighting the importance of a thorough and careful clinical examination in catching these cases early in their course.

Case presentation

A 33-year-old woman, known case of retinitis pigmentosa sine pigmento diagnosed since 5 years prior, came in for routine follow-up eye examination. She was maintained on vitamin A palmitate and reported no new visual symptoms at the time of examination.

On ophthalmological examination, the right eye had a best corrected visual acuity (BCVA) of 20/40−2, while the left eye had a BCVA of 20/30+2. Biomicroscopy identified a stable posterior subcapsular cataract on the right eye, while the left eye was unremarkable. The intraocular pressure was 12 mm Hg on both eyes. Funduscopy showed generalised mottled changes of the retinal pigment epithelium extending from the arcades toward the midperiphery devoid of bony spicule-like pigmentations, attenuated retinal vessels and waxy pallor of the optic discs on both eyes—all findings typical of retinitis pigmentosa sine pigmento (figure 1). However, there was a suspicious area of whitening on the superotemporal far periphery of the right eye. Fundus examination done with binocular indirect ophthalmoscopy with scleral depression, as well as slit lamp examination using fundus contact lenses, identified a 2-disc diameter-sized dome-shaped retinal mass with an overlying feeder vessel surrounded by hard exudates at the 11 o’clock far periphery, just adjacent to the pars plana (figure 2).

Figure 1.

Wide field fundus photograph of the right and left eyes showing mottled retinal pigment epithelium changes, attenuated retinal vessels and waxy optic disc pallor. The right eye has hazy media due to cataract. Note that the mass at the superotemporal periphery cannot be visualised even on wide field fundus photography. R, right; L, left.

Figure 2.

Slit lamp photograph of the fundus of the right eye using contact lenses. View through a Mainster lens (A) shows the dome-shaped retinal mass at the superotemporal periphery. Higher magnification through a Goldmann lens (B) better visualises the mass (bordered by dotted lines) associated with a dilated feeder vessel (white arrowhead) and surrounding exudates (yellow arrowheads).

Investigations

The patient’s ocular history was reviewed to ascertain the diagnosis of retinitis pigmentosa, since similar vessel attenuation and retinal changes can occur in other retinal conditions such as gyrate atrophy, choroideremia, cone-rod dystrophy, Leber congenital amaurosis, drug toxicity from chloroquine or thioridazine toxicity and infectious retinopathy from syphilis, rubella or diffuse unilateral subacute neuroretinitis. Review of ocular history revealed a history of nyctalopia affecting both eyes beginning when she was in her 20s, as well as progressive peripheral vision loss over the past few years. Full-field electroretinogram revealed reduction in both a-wave and b-wave amplitudes in both eyes (figure 3), consistent with a generalised retinopathy affecting both cones and rods, a pattern consistent with advanced retinitis pigmentosa. Perimetry revealed a ring scotoma in both eyes (figure 4), a pattern which also occurs in advanced retinitis pigmentosa.

Figure 3.

Full-field electroretinogram demonstrating reduction in both a-wave and b-wave amplitudes for both light-adapted and dark-adapted conditions.

Figure 4.

Perimetry demonstrating complete ring scotoma for both eyes. OD, right eye; OS, left eye.

Fluorescein angiography revealed a mild degree of vascular leakage with a background of chorioretinal atrophic window defects in the right eye. The left eye did not exhibit such leakage (figure 5). The mass lesion was too far in the periphery to visualised by angiography. Optical coherence tomography revealed mild atrophic changes in the photoreceptor and outer retinal layers of the macula in both eyes, with no cystoid macular oedema (figure 6).

Figure 5.

Fundus fluorescein angiography showing vascular leakage of the retinal vessels on the right eye. There was no leakage seen on the left eye. Note that both eyes exhibit background chorioretinal atrophic window defects. R, right; L, left.

Figure 6.

Optical coherence tomography scans showing mild outer retinal atrophy but otherwise normal macular structure on both eyes. R, right; L, left.

Ocular B-scan ultrasonography revealed a 2.81×3.03×3.01 mm retinal mass at the superotemporal periphery which exhibited mixed low to moderate echogenicity on A-scan. There was no adjacent subretinal fluid nor choroidal thickening (figure 7).

Figure 7.

Ocular ultrasonography on the right eye with transverse scanning at 11 o’clock reveals a 2.81×3.03×3.01 mm retinal mass (bordered by dotted lines) at the superotemporal periphery. The mass exhibits mixed low to moderate echogenicity on A-scan.

The patient was referred to an ocular oncologist. The findings of a vascular retinal mass in the periphery associated with retinitis pigmentosa were consistent with the diagnosis of a secondary retinal VPT.

Differential diagnosis

The major differential diagnoses of retinal vasoprolifetive tumours include other tumorous lesions of the retina and choroid, including amelanotic melanomas, amelanotic nevi, choroidal metastasis, capillary hemangiomas, Coats’ disease, peripheral exudative haemorrhagic chorioretinopathy and eccentric disciform lesions.

While other differential diagnoses were entertained, the constellation of findings in this case was more consistent with a secondary VPT. The tumour presented as a raised lesion with associated feeder vessel formation and exudative changes which are findings seen in vascular tumours. Its association with an underlying retinal condition (ie, retinitis pigmentosa sine pigmento) strengthened the suspicion. The appearance of the lesion on B-scan, although non-specific, was more consistent with a retinal tumour. Fluorescein angiography and optical coherence tomography would have been helpful in clinching the diagnosis had the lesion been located more posteriorly.

Treatment

After a thorough discussion with the patient, focal laser photocoagulation of the tumour was decided as the appropriate management. The tumour was completely bordered (figure 8) with laser marks using a combination of both conventional slit lamp and laser indirect ophthalmoscopy laser delivery systems. An argon green laser with a spot size of 150 μm was used, with the power set to 300 J and a duration of 150 ms and interval of 150 ms. A total of 248 shots were delivered around the tumour.

Figure 8.

Slit lamp photograph of the fundus of the right eye using contact lens after treatment with focal laser photocoagulation showing laser marks (white arrowheads) completely bordering the tumour.

Outcome and follow-up

The patient was monitored carefully after the laser procedure. At 6 months after treatment, there was no increase in size of the tumour and no signs of tumour activity. There was resolution of the exudative changes around the tumour as well as decrease in size of the tumour feeder vessel. The tumour body remained stable in size. There were no associated exudative changes in the macula and BCVA was stable.

Discussion

Retinal VPTs are benign vascular tumours of unknown origin. There is no sex predilection. They are usually diagnosed between the fifth and seventh decades of life but can be present at any age. Clinically, they appear as yellow-red, poorly defined retinal masses with a dilated feeding artery and draining vein.³ Pathological examination of these tumours reveals that they consist of mostly glial cells interlaced with a fine capillary network and dilated, hyalinised blood vessels, often with exudates, macrophages and foreign body giant cells. Since the histology is more consistent with a primary benign glial cell proliferation with secondary vasoproliferation rather than a neoplastic process, some authors have proposed the term ‘reactionary retinal gangliosis’ to be a more accurate term.⁴ These tumours are classified into primary (also idiopathic) and secondary types. In a series of 67 eyes with secondary retinal VPTs, underlying ocular conditions included retinitis pigmentosa (22%), pars planitis (21%), Coats’ disease (16%) and previous retinal detachment surgery (12%).^{3 5} The development of VPTs in these conditions is believed to be a reactive vascular response to different ocular insults.⁶

VPTs are classically located peripherally, usually in the inferotemporal quadrant. Although these tumours are benign, they can result in loss of vision related to various effects on the surrounding structures, including exudation, subretinal fluid, macular oedema, epiretinal membrane and vitreous haemorrhage. Although VPTs can potentially and profoundly affect visual function, visual acuity at presentation is 20/60 or worse in only 39% of patients.³ Subtle changes in vision may not be noticed by patients, particularly in the case presented where the patient had decreased visual acuity and constricted visual fields at baseline from underlying retinitis pigmentosa. In addition, the peripheral location of these tumours means they can be easily missed during routine examination by the ophthalmologist. Tumours often need to cause visual symptoms or reach a considerable size before they are brought to light to the clinician. The case presented highlights the difficulties in detecting these very small peripheral tumours. A thorough and astute clinical eye is needed.

Since literature on this topic have been limited to small case series or case reports, the indications for the treatment of retinal VPTs have not been clearly defined. Observation is often recommended for small, peripheral lesions with no apparent threat to vision. However, previous studies have shown that in treated patients with chronic exudative changes, improvement of visual acuity was not achieved despite regression of the tumour and resolution of intraretinal and subretinal fluid.⁷ These findings support treatment of early, small, asymptomatic lesions before the development of complications. Treatment modalities that have been employed for retinal VPTs include laser photocoagulation, transpupillary thermotherapy, verteporfin photodynamic therapy, plaque radiotherapy, and in some cases, resection of the tumour.⁷ In our case, the VPT was treated with argon laser photocoagulation with the goal of occluding the vascular supply of the tumour. Several studies have shown the efficacy of photocoagulation against small post-equatorial tumours.⁸ While the tumour in our case was very anteriorly located, adequate laser shots around the tumour were achieved using combination of a slit lamp and indirect ophthalmoscopy delivery systems. Several other modalities of treatment have been reported to be successful in the treatment of small VPTs. Cryotherapy using a triple freeze–thaw technique is often employed for more anteriorly located tumours, although repeated sessions may be required, especially for tumours with thickness exceeding 2 mm.⁷ Intravitreal anti-vascular endothelial growth factor agents been used alone or in combination with focal treatment with equivocal results in controlling the tumour and related oedema. Photodynamic therapy has recently been demonstrated to be effective.⁹ Radiotherapy with iodine-125 or ruthenium-106 has been shown to have regression rates of 97% and 72%, respectively, for relatively larger tumours.⁸

Learning points.

• Clinicians should be aware of the possibility of vasoproliferative tumour and other manifestations of exudative retinopathy occurring in patients with retinitis pigmentosa.

• Retinal vasoproliferative tumours can potentially result in vision loss from complications such as macular oedema, exudates, epiretinal membrane and vitreous haemorrhage.

• A careful examination of the peripheral retina should be done in patients with retinitis pigmentosa to identify such lesions.

• Laser photocoagulation can be effective against small retinal vasoproliferative tumours.