A 39-year-old female was referred for evaluation of a pigmented lesion in her left eye. Visual acuity (VA) was 20/20, and intraocular pressure measured 14 mmHg in both eyes. The refraction results indicated -9.5D in the right eye and 8.5D in the left eye. Anterior-segment examination of both eyes revealed normal findings.

The right fundus showed a tesselate fundus, along with peripapillary crescent atrophy. However, in the left eye, in addition to the tesselate fundus and peripapillary crescent atrophy, there was a yellowish-gray pigmented elevated lesion superior to the optic disc measured approximately 2-disc diameters. Additionally, a pigmented area was seen along the inferior arterial branch (Figure 1 A, B, and C).

Fluorescein angiography (FA) demonstrated hyperfluorescence throughout the lesion around the optic nerve with saccular dilation and leakage. Also, the lesion around the inferior branch showed hyperfluorescence due to staining (Figure 1D).

Swept-source optical coherence tomography (OCT) revealed retinal thickening on the nasal side of the fovea; an epiretinal membrane (ERM); a hyperreflective lesion in the inner retina, causing shadowing into the outer retina layers; and cystic changes in the outer retina. The fovea remained intact and the choroid appeared normal (Figure 1 E and F).

During follow-up, the ERM gradually thickened, resulting in heightened traction on the retina. As a consequence, retinal schisis and a full-thickness macular hole (MH) developed. Notably, the VA declined to 20/100 (Figure 2).

The patient underwent pars plana vitrectomy and membrane peeling. A negative staining technique with brilliant blue was used to identify the extent of the membrane. The ERM separation was done carefully to avoid bleeding. Intraoperative OCT was used to assess the retinal architecture. To address the main pathological issue and the continuous traction, we strategically placed an internal limiting membrane free-flap. After that, fluid-air exchange was performed slowly and 12% C₃F₈ tamponade was done, aiming for successful MH repair.

Remarkably, there were no complications during the surgery. The preretinal membrane was subsequently sent for pathology analysis, which revealed the presence of only benign pigmented cells (Video 1). 

One month after surgery, VA was 20/40, the MH was closed, and the retinal thickness decreased significantly (Figure 3). 

Discussion

Vision loss in combined hamartomas of the retina and retinal pigment epithelium (CHRRPE) results from several factors. These include preretinal fibrotic tissue, the presence of an ERM with associated tractional effects, choroidal neovascularization, and an increase in central macular thickness that is a phenomenon unrelated to the lesion’s location.¹ In peripapillary lesions, the thickening of the macula is primarily driven by the tractional effect of preretinal proliferation, leading to radiating retinal folds, vessel distortion, tractional macular retinoschisis, and retinal detachment. Early surgical intervention is beneficial for restoring retinal anatomy and improving VA. However, the impact of surgery on the hamartoma’s downward growth remains uncertain.^2,3 Notably, the prognosis for ERM without surgery is generally poor, with only 1 study reporting spontaneous detachment of the ERM.³

There are 4 large studies that showed the benefits of vitrectomy and membrane peeling in these cases. Cohn et al conducted a study involving 11 cases that underwent vitrectomy and membrane peeling, with or without the use of autologous plasmin enzyme. The outcomes observed included complete macular reattachment in all cases and vision improvement in 8 patients, stabilized vision in 3 cases, recurrence in 4 eyes, and the need for additional surgery in 3 patients.⁴

Sun et al reported that membrane peeling without plasmin injection led to retinal structure improvement in 100% of cases and visual improvement in 93%.⁵ Meanwhile, Gupta et al evaluated 12 cases, revealing visual improvement in 5, stable visual outcomes in 4, and vision loss in 3. Notably, the conventional predictors used for visual recovery after surgical removal of ERM do not fully explain the visual outcomes observed in CHRRPE.⁶

In a recent multicentric study, Ozdek et al investigated the effects of vitrectomy and membrane peeling in pediatric patients with retinal tumors. They divided 62 eyes into case and control groups. The study revealed that tumors located in the posterior pole, characterized by vascular tortuosity, distorted foveal contour, ellipsoid zone defect, and subretinal exudate, were associated with poor visual outcomes. Additionally, eyes that underwent surgery experienced a significant decrease in central macular thickness and improved VA. The authors emphasized the benefits of surgery in reducing retinal distortion for lesions located in zone 1 (in the macular and peripapillary areas) while suggesting observational management for lesions outside the posterior pole.⁷

Surgical challenges during ERM peeling along with CHRRPE include increased traction on retinal tissue leading to bleeding; however, identification of plane and careful separation of the ERM can avoid bleeding. Staining with dyes such as brilliant blue may help identify the extent of the membrane by negative staining. In this particular case, the presence of MH was unique along with CHRRPE, and considering the persistent traction due to the primary lesion, an assisted approach with the free-flap technique during primary repair was used, leading to successful closure.

Conclusion

Vitrectomy and membrane peeling surgery have demonstrated benefits for ERM-associated CHRRPE and associated retinal changes. A free-flap procedure with gas tamponade led to successful closure of this MH associated with CHRRPE.  

Elham Sadeghi, MD , is a clinical ophthalmology researcher in the department of ophthalmology at University of Pittsburgh School of Medicine in Pittsburgh, Pennsylvania. She reports no relevant disclosures. Reach her at elhams@upmc.edu.

Andrew W. Eller, MD , is a professor of ophthalmology in the department of ophthalmology at University of Pittsburgh School of Medicine in Pittsburgh, Pennsylvania. He reports no relelvant disclosures. Reach him at elleraw@upmc.edu.

Jay Chhablani, MD, is a professor of ophthalmology in the department of ophthalmology at University of Pittsburgh School of Medicine in Pittsburgh, Pennsylvania. He reports no relelvant disclosures. Reach him at chhablanijk2@upmc.edu.

References

1. Ledesma-Gil G, Essilfie J, Gupta R, et al. Presumed natural history of combined hamartoma of the retina and retinal pigment epithelium. Ophthalmol Retina. 2021;5(11):1156-1163. doi:10.1016/j.oret.2021.01.011

2. Zhang X, Yang Y, Wen Y, Xiao H, Peng J, Zhao P. Description and surgical management of epiretinal membrane due to combined hamartoma of the retina and retinal pigment epithelium. Adv Ophthalmol Pract Res. 2022;3(1):9-14. doi:10.1016/j.aopr.2022.09.001

3. Kumar V. Spontaneous separation of ERM in combined hamartoma of retina and retinal pigment epithelium. Ophthalmology. 2017;124(9):1402. doi: 10.1016/j.ophtha.2017.03.008

5. Sun LS, Raouf S, Rhee D, Ferrone PJ. Surgical outcomes of epiretinal membrane removal due to combined hamartoma of the retina and RPE. Ophthalmic Surg Lasers Imaging Retina. 2020;51(10):546-554. doi:10.3928/23258160-20201005-02

6. Gupta R, Ayachit A, Joshi S, et al. Optical coherence tomography analysis of surgical outcomes of combined hamartoma of retina and retinal pigment epithelium. Saudi J Ophthalmol. 2020;34(4):237-242. doi:10.4103/1319-4534.322614

7. Ozdek S, Ucgul AY, Hartnett ME, et al. Combined hamartoma of the retina and retinal pigment epithelium at pediatric age: surgical versus conservative approach. Retina. 2023;43(2):338-347. doi:10.1097/IAE.0000000000003652