First described by Wiethe in 1882,1 optic disc pit maculopathy is associated with subretinal and intraretinal fluid accumulation in continuity with an optic pit.2 Although multiple surgical approaches have been used to treat the detachment, the long-term visual prognosis is often poor.3 Equally enigmatic is the pathophysiologic basis of the disease; multiple hypotheses have been proposed. Post-enucleation histopathological specimens, though limited, have confirmed the presence of a plug of glial tissue in the base of the optic pit, which has been hypothesized to play a role in the development of neurosensory detachment.4 Herein, we describe the first clinicopathologic correlation of an optic pit plug excised at the time of pars plana vitrectomy (PPV).
A 31-year-old woman with no pertinent past medical history and an ocular history limited to LASIK and high myopia in both eyes presented with decreased vision in the right eye for 1 month. Best-corrected visual acuity (VA) was 20/25 in the right eye and 20/20 in the left eye. Anterior segment examination showed LASIK flaps in both eyes. The posterior examination disclosed an inferotemporal optic disc pit with communicating subretinal fluid in the right eye but was normal in the left eye. Optical coherence tomography (OCT) of the retinal nerve fiber layer (Figure 1A) and the macula (Figure 1B) showed subretinal and intraretinal fluid tracking from the inferotemporal optic pit. Fluorescein angiography (Figure 1C) showed pooling within the area of the pit. The patient was initially observed for possible spontaneous resolution of the optic disc pit maculopathy.
Multimodal imaging of the optic disc pit. (A) Optical coherence tomography (OCT) of the retinal nerve fiber layer (RNFL) shows a large optic pit in the right eye in the inferotemporal portion of the disc. (B) OCT of the retina in the right eye shows subretinal and intraretinal fluid along with schisis tracking from the disc. (C) Fluorescein angiogram of the right eye shows hyperfluorescence with pooling in the optic disc pit. (D) OCT of the retina in the right eye shows persistent subretinal and intraretinal fluid as well as photoreceptor shagging 5 months after initial presentation.
Five months later, the patient reported worsening vision and distortion in the right eye. Visual acuity had declined to 20/50. OCT displayed more prominent subretinal fluid and persistent intraretinal fluid (Figure 1D). A PPV with internal limiting membrane (ILM) peeling using indocyanine green (ICG) dye for visualization was performed. During the procedure, a glial plug was peeled from the inferior portion of the optic cup where the pit was located. A fluid air exchange was performed, and light laser was applied at the optic nerve margin in the region of the optic pit. No retinotomy or drainage of subretinal fluid was performed. A 20% mixture of SF6 gas was flushed through the vitreous cavity at the conclusion of surgery.
Histopathological examination of the glial plug showed fibrovascular neural tissue and spindle-shaped cells, which stained positively for glial fibrillary acidic protein, smooth muscle actin, and cluster of differentiation 31 (Figure 2).
Histopathological analysis of the optic pit plug. (A) Examination discloses dense central fibrovascular tissue with surrounding glial tissue. (Hematoxylin-eosin, original magnification x 200). (B) Examination discloses glial tissue surrounding fibrovascular tissue (Glial fibrillary acidic protein, original magnification × 200). (C) Examination discloses endothelial lined blood vessels (black arrows) present in the central dense tissue (CD31, original magnification × 400). (D) Examination discloses foci of smooth muscle differentiation within the fibrovascular tissue (Smooth Muscle actin, original magnification × 200).
Two months postoperatively, the patient presented with persistent blurry vision. VA measured 20/400 and OCT showed no resolution of subretinal fluid (Figures 3A and 3B). A second PPV with placement of a drainage retinotomy at the lowest intersection between the fluid pocket and the optic nerve was performed. Fluid-air exchange was performed and included laser application at the site of a draining retinotomy and 20% SF6 gas. Three months later, visual acuity improved to 20/100. Fundus examination disclosed scarring around the site of the optic pit and previous retinotomy (Figures 3C and 3D). OCT showed improvement in subretinal fluid (Figures 3E and 3F).
Multimodal imaging of the optic disc pit after removal of the glial plug. (A) Optical coherence tomography (OCT) of the retina and through the optic nerve (B) show persistent subretinal and intraretinal fluid. (C, D) Color fundus photographs show peripapillary and macular scarring around sites of photocoagulation and the macular retinotomy. (E, F) OCT of the macula shows improvement in subretinal fluid and atrophy after the second surgery.
This study demonstrates histopathologically that the embryological origin of the pit plug appears to be both glial and vascular. Of note, an anomalous Cloquet's canal may be seen terminating at the margin of an optic pit5 implying that the vascular elements may be an embryologic precursor. Hirakata et al conducted histopathologic analysis of an excised hyaloid strand in an anomalous Cloquet's canal at the optic disc pit.6 Electron microscopy showed clusters of collagen fibers but the specimen was markedly acellular, avascular, and not of neural origin, unlike the specimen in our case. The findings in the current study are more consistent with the optic pit formation hypothesis proposed by Gregory-Roberts et al.7 that the remnant may represent a disruption of normal embryological development that typically ends with atrophy of the primitive glial cells and blood vessels that form the Bergmeister papilla on the surface of the developing optic disc.
The optic disc pit has been observed clinically to contain interlacing glial tissue.2,8–12 In a histopathologic study of enucleated eyes by Ferry, the optic pits in several cases were found to be filled with glial tissue interspersed with blood vessels as well as retinal pigment epithelium, with some glial elements projecting anteriorly from the surface of the pit.4 Ferry proposed that gradual contraction of glial tissue enveloping retinal nerve fibers might lead to tractional forces and that the glial proliferation was a pathologic response to atrophy. These studies did not include immunohistopathologic evaluation, however. Another hypothesis is that the glial plug is not actually an etiologic factor suggesting traction, but rather a secondary phenomenon from the optic pit gaping enough to stimulate and signal for glial proliferation.
The pathogenesis of neurosensory retinal detachment associated with an optic disc pit remains unproven. Multiple theories have been proposed. A connection has been postulated between the vitreous cavity and subarachnoid space,13–15 and, accordingly, that the origin of the subretinal fluid is cerebrospinal fluid (CSF). This theory has been supported by biochemical analysis of the fluid drained from the pit and macular detachment which demonstrated composition similar to CSF.16 Another postulate is that liquefied vitreous accesses the subretinal space via the pit.17–19 A third hypothesis is that vascular leakage near the pit produces the fluid.20 Investigators have also hypothesized that the fluid may be either of vitreous or cerebrospinal origin, but that the critical element is a scleral or lamina cribrosa defect, which allows for anomalous communications between the intraocular and extraocular spaces resulting in fluid migration under certain pressure gradients.21 A final theory is based upon vitreous traction, which can be approached surgically.22
Despite the incomplete understanding of pathogenesis, and hence surgical rationale, successful resolution of fluid has been affected with a variety of surgical techniques aimed at relieving traction, creating a barrier in the flow of fluid between the pit and the macula, and internal drainage of fluid. Permutations include gas tamponade, ILM peel,23 intraoperative drainage of subretinal fluid through the macula or directly from the pit,24 laser photocoagulation at the peripapillary border, or combinations of these.25 There is no consensus on surgical strategy.
A glial plug has been observed clinically in a large proportion of optic pits26 and might argue for a tractional mechanism for maculopathy. Hasegawa et al.27 showed in vivo that eye movements created traction originating from a tissue terminating at the base of the pit. Yet, although removal of the glial plug may result in a decrease in tractional forces and favorable anatomic outcomes, it does not appear mandatory for resolution of subretinal fluid.7 On the other hand, it cannot be ruled out that the glial plug is merely a secondary phenomenon whose substrate might be the cells in the pit.
In summary, this histopathological analysis and molecular pathology case study demonstrates the pit plug to be of neurologic and vascular origin. The etiology of the glial plug and its role in the development of maculopathy remain uncertain, but the lack of complete resolution with its removal vitiates a central role in pathogenesis or therapy.
- Wiethe T. Ein Fall von angeborener Difformitat der Sehnervenpapille. Arch F Augenh. 1882;11:14–19.
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- Hirakata A, Hida T, Wakabayashi T, Fukuda M. Unusual posterior hyaloid strand in a young child with optic disc pit maculopathy: Intraoperative and histopathological findings. Jpn J Ophthalmol. 2005;49(3):264–266. doi:10.1007/s10384-004-0185-5 [CrossRef]
- Gregory-Roberts EM, Mateo C, Corcostegui B, et al. Optic disk pit morphology and retinal detachment: Optical coherence tomography with intraoperative correlation. Retina. 2013;33(20):363–370. doi:10.1097/IAE.0b013e318263d0a6 [CrossRef]
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