Intraocular Pressure Lowering Associated with Worsening Optic Pit-Like Retinoschisis

Abstract

We present a case of optic pit-like macular retinoschisis in the absence of advanced glaucomatous cupping. Intraocular pressure (IOP)-lowering therapy, which was started due to an early concern for glaucoma, caused a worsening of the retinoschisis, which subsequently resolved upon discontinuation of the IOP-lowering therapy. Lower IOP likely triggered intraretinal fluid accumulation by facilitating a translaminar gradient from the subarachnoid to intraretinal space.

Introduction

Optic disc pit maculopathy or optic pit-like macular retinoschisis with or without a glaucomatous nerve involves accumulation of intraretinal fluid at Henle’s layer, postulated to originate from connections between the intraocular and extraocular spaces across the lamina cribrosa.¹ It has been hypothesized that the intraretinal fluid in this condition originates from either the vitreous cavity or subarachnoid space, which largely depends on whether the lamina cribrosa and connective tissue capsule is permeable or not.¹ We present a case of optic pit-like macular retinoschisis that worsened after topical ocular anti-hypertensive treatment and resolved with removal of the medication, providing further support to the idea that optic pit-like macular retinoschisis requires a pressure gradient between the intracranial and intraocular space.

Case Report

A 70-year-old male evaluated by our comprehensive ophthalmology clinic was found to have optic nerves of approximately 1.8 mm in the right eye and 1.7 mm in the left eye without pits but with deep optic cups and symmetrically enlarged cup:disc ratios of 0.7. Humphrey visual field revealed mild arcuate defects in both eyes. In both eyes, visual acuity was 20/30 with a refraction spherical equivalent of +3.50 and +3.00 in the right and left eye, respectively, and intraocular pressures were 18 mmHg by iCare. There was no anterior or vitreous cell, nor any other signs of ocular inflammation. Optical coherence tomography (OCT) of the macula in the left eye revealed nasal macular retinoschisis (Figure 1A). The cause of the retinoschisis was undetermined. Notably, the patient had no past ocular surgical history, he was not diabetic, there was no evidence of vitreoretinal adhesion nor impending posterior vitreous detachment (PVD), and he was hyperopic (rather than myopic). He was labeled a glaucoma suspect and started on latanoprost 0.005% in each eye at bedtime.

Figure 1. Evolution of Macular Retinoschisis On and Off Intraocular Pressure Lowering Medications.

Macular OCT horizontal raster images taken at (A) initial visit, (B) 8 months after starting latanoprost, and (C) 7 months after stopping latanoprost, showing fluctuating intraretinal fluid in the outer plexiform layer more than the inner nuclear layer. Poor optical quality is due to a concurrent cataract.

Eight months after starting latanoprost, the patient was referred to our retina clinic for the nasal macular retinoschisis. At this visit, visual acuity was 20/30 in the right eye and 20/50 in the left. Intraocular pressures were 13 and 11 mmHg by iCare. OCT of the left macula revealed worsened retinoschisis threatening the fovea (Figure 1B) with an enlarged cup:disc ratio and peripapillary atrophy, but without evidence of an optic pit (Figure 2). The patient’s latanoprost was discontinued given concern that the nasal macular retinoschisis was the result of translaminar flow from the subarachnoid space via an optic pit-like mechanism. On follow-up visits, IOP varied between 14-20 mmHg, increased from 11 mmHg while on latanoprost, and visual acuity improved to 20/30 (limited by cataracts). The macular retinoschisis significantly improved 7 months after discontinuation of latanoprost (Figure 1C).

Figure 2. Red Reflectance Photo of Culprit Optic Disc.

Taken 8 months after starting latanoprost, the photo demonstrates nasal macular elevation and optic disc cupping with peripapillary atrophy but no sign of an optic pit.

Discussion

Optic pit-like macular retinoschisis that originates at the optic nerve is thought to be due to a combination of two factors: 1) a defect in the lamina cribrosa, allowing communication between the subarachnoid space and the intraocular space and 2) a translaminar pressure gradient in which intracranial pressure (ICP) is greater than IOP. In such a scenario, fluid in the subarachnoid space or accumulated retrolaminar vitreous fluid can pass through defects in the lamina cribrosa and split the nasal macula at the level of Henle’s layer. Classically, the defect in the lamina cribrosa is an optic pit, and the entity is therefore known as optic pit maculopathy. However, advanced glaucoma or even just a deep optic cup can also presumably cause defects in the lamina cribrosa, triggering an optic pit-like maculopathy without a frank pit.² For example, Fujimoto et al. described a case series of patients with macular retinoschisis from the optic disc without a visible optic pit or advanced glaucomatous cupping (No Optic Pit Retinoschisis [NOPIR]).³ Interestingly, all patients in this case series had peripapillary atrophy, which may have further allowed fluid to pass through a small laminar defect and access the outer plexiform layer (OPL).

Here, we present a case of NOPIR in a patient with a deep optic cup and peripapillary atrophy in which the patient’s macular retinoschisis worsened with ocular antihypertensive medication use and improved after discontinuation of the antihypertensive. This provides convincing data that optic pit and optic pit-like maculopathies progress when the intracranial/subarachnoid/retrolaminar pressure, which normally runs between 5 and 20 mmHg, exceeds IOP. We have illustrated this mechanism in Figure 3. We postulate that the patient’s deep cup and peripapillary atrophy both provided opportunities for microscopic disruptions in the intricate organization of axons and connective tissues of the lamina cribosa to allow communications with the OPL.

Figure 3. Diagram Illustrating Optic-Pit Like Macular Retinoschisis.

Demonstration of a deep optic cup along with peripapillary atrophy, which can cause laminar defects allowing fluid to seep into the outer plexiform layer (OPL) of the retina. In this diagram, the source of intraretinal fluid is deemed to be CSF, but it is also possible for vitreous fluid to gain access to the retrolaminar space and then seep into the OPL, as illustrated by Jain and Johnson in 2014.¹ IPL = Inner Plexiform Layer, INL = Inner Nuclear Layer, OPL = Outer Plexiform Layer, ONL = Outer Nuclear Layer, RPE = Retinal Pigment Epithelium, IOP = Intraocular Pressure, ICP = Intracranial Pressure

After discontinuation of the latanoprost, the patient’s visual fields remained stable, allowing him to remain off IOP-lowering medications. However, in patients with optic pit or optic pit-like maculopathy with concurrent glaucoma, systemic or topical carbonic anhydrase inhibitors (CAIs) could serve as a more viable option to lower IOP.^1,4 This is due to CAIs’ effects on not only lowering IOP, but ICP as well, which would theoretically decrease the translaminar gradient of flow between the retrolaminar/subarachnoid and prelaminar spaces. In addition, CAIs can modulate RPE pump function, which can decrease macular fluid.⁵

Interestingly, a schisis cavity’s response to IOP changes appears to depend on the cause of the schisis. Other types of macular retinoschisis worsen with IOP elevation (such as retinoschisis in the RNFL layer usually seen in glaucoma as well as myopic retinoschisis).^6,7 However, when the schisis is predominantly located in Henle’s layer—the only layer that exhibits a connection to the subarachnoid space—it appears that schisis improves with an increase in IOP. Similar to our case, Markopoulos et al. describe a patient who presented with hypotony and macular retinoschisis in Henle’s layer that resolved with increase in IOP.⁸

We considered the possibility that the macular fluid in our case originated from other causes. The patient was not diabetic, myopic, or post-operative, ruling out diabetic macular edema, myopic traction maculopathy, or Irvine-Gass. Physical exam and OCT revealed no vitreomacular traction, evolution of a PVD, or inflammation, ruling out hyaloidal traction or uveitis as the cause of the macular fluid. Latanoprost itself has been linked to macular edema secondary to prostaglandin-induced vascular leakage, but we consider this mechanism to be less likely to cause the findings in the patient described here.⁹ Prostaglandin-induced vascular leakage, which is thought to also mediate macular edema in Irvine-Gass, is centered around the fovea and has a cyst-like configuration to the fluid.^9,10 In contrast, the patient described here had purely nasal macular schisis, classic for optic-pit like maculopathy, and the fluid, especially in the inner nuclear layer, was slit-like rather than cystic, consistent with schisis seen in optic-pit like maculopathy rather than fluid from vascular leakage.³ Finally, we note that the patient received latanoprost in both eyes, but only developed the schisis in the left eye, making it more likely that the mechanism of macular schisis was due to latanoprost’s IOP-lowering effects in an eye with pre-existing NOPIR rather than due to vascular-leakage inducing effects, which we would expect to see in both eyes. To be absolutely certain vascular leakage from latanoprost did not contribute to the patient’s worsening macular schisis, a fluorescein angiogram could be obtained.

In summary, our case presents strong supporting evidence that optic pit and optic pit-like maculopathies, also known as NOPIR, require a translaminar pressure gradient to manifest. The lamina cribrosa forms the border between the intraocular space (which has a higher pressure) and the retrobulbar space (which has a lower pressure). When this pressure gradient reverses—in our case via addition of an IOP-lowering medication—fluid can exit the subarachnoid space through breaks in the lamina cribrosa and track into the macula via the OPL.