PEDIATRIC MACULAR HOLE ASSOCIATED WITH VITREORETINAL TRACTION ON EPIRETINAL LESIONS: A CASE REPORT AND LITERATURE REVIEW

In this study, we present a pediatric nontraumatic full-thickness macular hole. After a short period of observation, surgery achieved anatomic success and significantly improved VA. The etiology was related to vitreoretinal traction associated with numerous epiretinal lesions, which contained only internal limiting membrane (ILM) fragments on histologic examination.

Abstract

Purpose:

We describe a case of nontraumatic macular hole in a pediatric patient associated with numerous epiretinal lesions throughout the macula.

Methods:

A healthy 9-year-old girl presented to retina clinic with several months of blurry vision in the right eye. Clinically, there was a full-thickness macular hole with serous detachment and white epiretinal tufts. Spectral-domain optical coherence tomography confirmed the presence of the full-thickness macular hole with hyperreflective epiretinal proliferations in the right eye and an unremarkable left eye. Systemic workup was negative. After a short period of observation, the patient underwent vitrectomy with internal limiting membrane peel and 14% C3F8 gas tamponade in the right eye. Multiple intraoperative samples were sent for further testing, which were also negative.

Results:

At 1- and 12 months/1 year postoperative visits, examination showed successful closure of the full-thickness macular hole with resolution of the subretinal fluid and improved VA.

Conclusion:

Nontraumatic macular holes in pediatric patients warrant systemic and ocular workup, including fluorescein angiography and laboratory testing. Good anatomic and visual outcomes are generally seen with spontaneous and surgical closures of macular holes in this age group. Early vitrectomy with histologic analysis of ocular samples should be considered in pediatric macular hole cases associated with vitreoretinal traction, especially those with epiretinal abnormalities.

Macular holes are an uncommon entity in the pediatric population, with most cases occurring because of trauma.¹ Other previously described causes of pediatric macular holes include X-linked retinoschisis, incontinentia pigmenti, retinopathy of prematurity, ocular toxocariasis, optic pit, and high myopia.² The remainder of causes are presumed to be idiopathic or because of rare etiologies mostly described in case reports. Herein, we describe a case of a pediatric full-thickness macular hole with the presence of numerous epiretinal lesions and associated vitreoretinal traction.

Case Report

A healthy 9-year-old girl presented to retina clinic with several months of blurry vision in the right eye. She had no ocular or medical history, and she had an unremarkable family ocular history. She had no history of trauma, which was also confirmed by her parents. Although she was a gymnast, she denied any significant falls or head injuries in the recent past. She had an indoor full-grown cat, and her last travel was to Mexico several months before presentation.

Ocular examination was relevant for 20/150 vision in the right eye compared with 20/20 in the left eye. She had symmetric, age-appropriate, low hyperopia of +1.0D in both eyes, but refractive correction failed to improve vision in her right eye. She had normal pupils and intraocular pressures in both eyes. Slit lamp examination of the right eye showed a deep and quiet anterior chamber and quiet anterior vitreous. Fundus examination revealed a full-thickness macular hole with a well-circumscribed macular detachment associated with a central white tuft and several small white epiretinal tufts parafoveally in the right eye (Figure 1A). The hyaloid was still attached and there were no hemorrhages. Complete peripheral examination with scleral depression showed a flat retina with no retinal tears, but she had several chronic appearing atrophic perivascular chorioretinal scars inferonasally in the right eye. The examination and imaging of the left eye were entirely normal (Figure 1B).

Fig. 1.

Fundus photography and angiography of both eyes. A. Fundus photograph of the right eye shows a well-circumscribed macular detachment with central white tuft and several small white epiretinal tufts parafoveally with a full-thickness macular hole. B. Fundus photograph of the left eye shows an unremarkable posterior pole. C. Fluorescein angiography (FA) shows pinpoint staining of the vitreoretinal tuft at the opening of the macular hole. There is mild staining inferonasally in areas of chorioretinal perivascular atrophy. D. FA is normal in the left eye. E. Higher magnification of FA image of right posterior pole (late phase) demonstrates no leakage from the epiretinal lesion. F. Fundus autofluorescence of the right eye shows multiple macular pinpoint hyperautofluorescent spots and hyperautofluorescence superior to the inferior arcade, the latter correlating with the area of pooling fluid in the inferior macula.

There was no associated snowbanking, snowballs, or vascular sheathing in either eye. The optic nerves were unremarkable and without edema, hemorrhage, or pallor. Fluorescein angiography (Figure 1, C–E), fundus autofluorescence (Figure 1F), and optical coherence tomography (OCT) (Figure 2) were performed, confirming the macular detachment and demonstrating rare cell in the posterior vitreous in the right eye. The fluorescein angiography showed staining without associated leakage of the largest central epiretinal lesion and of the peripheral chorioretinal lesions in the right eye and was normal in the left.

Fig. 2.

Preoperative OCT of the right eye. A. Heat map showing significant central macular thickening. B–D. Cross section images showing a full-thickness macular hole (arrow, B) associated with epiretinal lesions with a large tuft present at the opening of the macular hole and attached to the vitreous (asterisks, C). These images demonstrate central subretinal fluid with shaggy photoreceptors and mild vitreous cells in the posterior vitreous.

Given the appearance of the epiretinal tufts and the presence of vitreous cells on OCT, an infectious, infiltrative, and inflammatory workup was performed, including urinalysis and several serum studies: complete blood count, comprehensive metabolic panel, angiotensin-converting enzyme, lysozyme, beta-glucosidase, toxocara, toxoplasma, bartonella, syphilis, lyme, quantiFERON, coccidioides, blastomyces, histoplasma, coxsackie, herpes simplex virus types 1 and 2, Epstein–Barr virus, and varicella zoster virus. Serology was positive for herpes simplex virus 1 IgG, varicella zoster virus IgG, and Epstein–Barr virus IgM, while the remainder of the workup was negative.

We elected at that time to medically manage the macular detachment using dorzolamide three times per day in the right eye. At her 2-month follow-up visit, there was mild improvement of VA to 20/80, but persistent subretinal fluid and epiretinal tufts. A decision was then made to pursue surgical management to avoid long-term sequelae of the macular detachment. A pars plana vitrectomy with vitreous biopsy, internal limiting membrane (ILM) peel, aided with diluted indocyanine green, air–fluid exchange, and 14% C3F8 gas tamponade was performed in the right eye. Intraoperatively, there was a large juxtafoveal epiretinal white lesion that had been under traction previously that seemed more mobile after segmentation from vitreoschisis release. There was a central full-thickness macular hole that was noted intraoperatively to be a full-thickness horseshoe tear along the inferior aspect of the white central lesion (corresponding to Figure 2B). There was an adjacent smaller lesion with a pinpoint hole present. There were multiple small white epiretinal lesions present through the temporal paracentral macula. The ILM was grasped using Finesse Sharkskin forceps and peeled out to the arcades. The tissue fragments were then placed in formalin and sent for histopathology examination. The samples obtained are detailed in Table 1, and microbiologic analysis of these samples was negative. Pathology reported the epiretinal proliferation to be PAS-positive basement membrane material consistent with ILM fragments without evidence of acute, chronic, or granulomatous inflammation, neoplasm, or presence of any inflammatory cells (Figure 3).

Table 1.

Intraocular Samples Sent for Diagnostic Testing

Sample	Content(s)	Volume	Indication
1	ILM tissue, tissue biopsies, in formalin and wrapped in blue paper	n/a	- Review for granulomatous disease, inflammation, infectious organisms - Review for possible Gaucher cells - Review for retinoblastoma cells (atypical)
2	Undilute vitreous	n/a	Microbiology*
3
a	Slightly dilute vitreous	2-3cc	Pathology
b		2-3cc	Microbiology*
4	Vitreous cassette, in no fixative, wet ice to keep cool and delay acellular degeneration	250cc	Pathology
5	Aqueous humor	100-200 µL	Microbiology*

^*Fungal smear and culture, Acid Fast Bacillus smear and mycobacterial culture, gram stain and bacterial culture, broad range 16S polymerase chain reaction (PCR), fungal broad range PCR, BHOLD (stored for further testing), PCR of histoplasma, Blastomyces, varicella zoster virus, herpes simplex virus, cytomegalovirus, bartonella, and toxoplasma.

Fig. 3.

Representative histopathologic image of the intraoperative samples. High-magnification (×40) image demonstrates PAS-positive thin membranous tissue folded on itself and consistent with internal limiting membrane (ILM).

The patient had an uncomplicated postoperative course with good compliance with drops and positioning. At her 1-month postoperative visit, her OCT macula showed a closed macular hole with resolution of the subretinal fluid and early reconstitution of the ellipsoid zone. Her vision progressively improved, and at her last follow-up, 1 year after surgery, vision had improved to 20/40. The most recent OCT macula revealed absence of subretinal fluid, but there was persistence of a few intraretinal hyperreflective deposits (Figure 4).

Fig. 4.

Comparison of optical coherence tomography (OCT) images pre- and postsurgical intervention. A. Preoperative en face image depicting the macular serous retinal detachment, which corresponded to a best corrected visual acuity of 20/150. B. Postoperative en face image at 1 year after surgery, showing resolution of the subretinal fluid and corresponding to a visual acuity of 20/40. C. OCT cross section 1 year after surgery shows resolution of the subretinal fluid with the persistence of rare intraretinal hyperreflective deposits (arrow).

Discussion

Pediatric Macular Holes

Pediatric macular holes are rare and much less common than their counterpart in the adult population.^1,2 Although macular holes in adults are mostly idiopathic and related to vitreoretinal traction, trauma is the most frequent underlying etiology in children.¹ Other pediatric macular hole causes reported in the literature include laser injury, inherited retinal diseases, retinopathy of prematurity, ocular infections, high myopia, and optic nerve abnormalities.^1,2 Case reports have also described associations with familial exudative vitreoretinopathy,³ Coats disease,⁴ Bartonella neuroretinitis,⁵ choroidal coloboma,⁶ epiretinal membrane,⁷ retinal dystrophies and degenerations,^8,9 and incompletely regressed Bergmeister papilla or persistent fetal vasculature.¹⁰ Although trauma was considered initially as a potential cause as our patient is a young gymnast, the presence of epiretinal proliferation was atypical for trauma. Furthermore, the patient denied any significant trauma during her training. Other considerations were neurofibromatosis and combined hamartoma, but the patient had no associated systemic manifestations and no retinal disorganization on OCT imaging. The intraoperative appearance of the hole pointed to vitreoretinal traction as the cause of the macular hole that developed in a curvilinear fashion around a large central epiretinal lesion.

The management of full-thickness macular holes in children remains controversial. Spontaneous closure, notably of traumatic cases, has been previously reported.² As such, many surgeons have elected for watchful waiting of pediatric macular holes, with variable duration ranging from a few months up to a year. Kothari, et al reported a range of observation of 5–369 days in their study.³ Mitamura, et al observed 11 eyes with traumatic holes, 8 of whom were patients younger than 18 years of age, for a variable period of up to 12 months.⁴ Four cases, including one child, underwent pars plana vitrectomy after several months of observation because of enlarging macular hole or vitreous hemorrhage. They noted that spontaneous closure was more likely with younger patient age, smaller macular holes, and absence of posterior vitreous detachment.⁴ However, larger macular holes were also reported to show spontaneous closure.² Other physicians elect to operate earlier without any period of observation.^1,5

Despite the absence of consensus on this topic and because of historical presence of spontaneous closure with initial observation, watchful waiting might be considered, especially if the macular hole diameter and the subretinal fluid are noted to be decreasing, keeping in mind the risk of amblyopia in the pediatric population.² Currently, shorter periods of observation are being adopted, though there is no consensus on the recommended length of time.³ Because our patient showed no decrease in the diameter of the macular hole nor resolution of the associated retinal detachment, we elected to operate after 2 months of observation.

Different surgical procedures have been described, with similar general approach to adult macular hole, but with much more challenging posterior vitreous detachment induction. To induce posterior vitreous detachment during surgery for our patient, several layers of retinoschisis, visualized well with 1:5 diluted triamcinolone, were identified and peeled. Our literature review found that for primary surgery, pars plana vitrectomy with ILM peeling and internal tamponade were typically done.^1,2,6 Minor variations in technique included the use of dye for the peel and the use of different tamponading agents: gas, most commonly, but also silicone oil or air.^2,3 Silicone oil was infrequently used, mostly in cases where positioning would be an issue,⁷ or when associated with complex retinal detachment.²

Ghoraba, et al compared silicone oil with C3F8 tamponade in traumatic macular hole repair, which included pediatric and adult cases. However, all patients included in this study younger than 19 years had silicone oil injection. They concluded that gas was more effective at achieving initial closure, with fewer reoperations and better VA.⁶ In general, the rate of closure after primary procedure in pediatric macular hole was high,³ ranging from 75.9%² to 100% in smaller case series.⁵ In cases of nonclosure, and sometimes as part of primary surgery as well, adjuvant procedures may be used, including fresh blood coating, platelet concentrate, TGFß2 (historically), insertion of the ILM flap, autologous ILM transplant, or a lens capsular flap into the macular hole, and Tano brushing to oppose the edges of the macular hole. Secondary surgeries might also include enlarged ILM peeling with blood coating and repeat ILM peeling if found to have incomplete initial peeling.^2,3 Good anatomic and visual results were seen with both spontaneous and surgical macular hole closure.^2,3

Epiretinal Proliferation and Tufts

Several studies have documented the presence of epiretinal proliferation and/or tufts in adults and children. However, this is still an uncommon entity with a wide array of differential diagnoses.⁸ These include inflammatory and infectious uveitides, vitreoretinal lymphoma, Gaucher disease, familial exudative vitreoretinopathy, and postsurgical or postintravitreal injection deposits.^8–10 However, these are usually associated with other clinical findings, including a history of prior ocular disease or procedures, retinitis/chorioretinitis, vitreous cells, and/or associated systemic manifestations, none of which were present in our patient. In addition, all blood and ocular samples returned negative.

In conclusion, this case illustrates the occurrence of a full-thickness macular hole in a child with no history of trauma and no other concerning ocular findings. After limited period of watchful waiting, surgical approach proved successful with anatomic restoration and improvement in VA. Idiopathic epiretinal proliferation, noted to be ILM histologically, was associated with vitreoretinal traction and macular hole in this patient. Early vitrectomy should be considered in pediatric macular hole cases with significant vitreoretinal traction, and the wide range of pediatric macular hole etiologies should be considered and ruled out, when appropriate, when evaluating these pediatric patients.