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Routine exam reveals thinning GCC
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A 58-year-old Caucasian man presented to the clinic for a comprehensive eye exam and contact lens evaluation. He denied any visual complaints with his habitual glasses and soft disposable contact lenses.
His ocular history included a single episode of bilateral episcleritis that resolved after a course of ophthalmic steroid drops. Except for a complaint of sore joints, there was no other significant reported medical history or family ocular history. He was taking no medications. His only known drug allergy was to Aleve (naproxen sodium).
At evaluation, distance visual acuity with monovision contact lenses was 20/20 OD and 20/60 OS, improving to 20/20 with over-refraction. Alternating cover test revealed orthophoria at distance and near. Local and global stereopsis was normal. Color vision was normal as measured binocularly by Ishihara plates. Final refraction in the right eye was +1.25 sph (acuity 20/20) and left eye was +1.25 D -0.25 D x 082 (acuity 20/20).
Both pupils were round, equal and reactive to light without signs of relative afferent pupillary defect. Confrontation fields were full to finger counting in the right and left eyes, and ocular motility of each eye showed no restrictions. Blood pressure was 132/88 mm Hg. BMI was calculated to be 23.7 (normal). Macular pigment optical density (MPOD) was 0.58 density units (above average). Slit lamp examination of the anterior segment was unremarkable. IOP was 20 mm Hg OD and 18 mm Hg OS.
Screening spectral domain OCT (SD-OCT) macular screening scans during initial exam work-up showed abnormal thinning of the macular ganglion cell complex (GCC), especially to the nasal side of the macula, along with normal retinal thickness and structural B scans in both eyes. Stereoscopic fundus exam of both eyes confirmed clinically normal maculae and retinal vasculature. The optic nerves in both eyes consisted of average-sized discs with slight scleral crescents. There was subtle suggestion of poor perfusion as evidenced by apparent pallor of the temporal neural rim of each optic nerve. The optic nerve cup-to-disc ratio was 0.5 in the right eye and 0.4 in the left eye. The peripheral retina was flat and intact 360 degrees in each eye without conditions predisposing to retinal detachment. Anterior segment examination confirmed open angles and was unremarkable bilaterally.
What’s your diagnosis?
See answer on the next page.
Based on the clinical findings, differential diagnoses included the following potential causes of bilateral optic neuropathy: glaucoma, neurodegenerative (multiple sclerosis, Alzheimer’s disease, Parkinson’s disease), inflammatory (demyelinating diseases such as multiple sclerosis or neuromyelitis optica), inflammatory (non-demyelinating diseases such as posterior uveitis, orbital inflammatory pseudotumor, sarcoidosis, Behcet’s inflammatory bowel, systemic lupus erythematosus, Sjögren’s syndrome, Wegener’s granulomatosis), ischemic (arteritic or nonarteritic), infectious (Lyme’s disease, cat-scratch fever, syphilis), infiltrative (lymphoma, leukemia, multiple myeloma, carcinoma), compressive (thyroid, meningioma, pituitary adenoma, intracranial aneurysm, craniopharyngioma, gliomas of anterior visual pathway), hereditary (Kjer’s, Leber’s), toxic-nutritional (medication side effect, methanol abuse, vitamin deficiencies), radiation exposure to brain or orbit, traumatic, paraneoplastic (from small cell lung cancer), congenital optic nerve hypoplasia (microdisc) and optic disc drusen.
In addition, studies have shown that the following systemic diseases could also cause thinning of the optic nerve retinal nerve fiber layer (RNFL) and GCC as measured by SD-OCT: obstructive sleep apnea, diabetes, fibromyalgia, chronic migraines, mild cognitive impairment, frontotemporal dementia, stroke, posterior cerebral artery infarction, small vessel cerebral ischemia, cerebral ischemic lesion, post-geniculate neurologic disease, multiple system atrophy, amyotrophic lateral sclerosis (ALS), HIV, Wilson’s disease, smoking, chronic obstructive pulmonary disease, tuberous sclerosis complex, epilepsy, neuropsychiatric (schizophrenia, bipolar disorder), traumatic brain injury, cluster headaches and internal carotid artery occlusion.
Working through the differentials
The symmetrical presence of GCC thinning nasal to the macula that crosses the horizontal raphae combined with lack of neural rim thinning, elevated IOP or narrow angles made a diagnosis of glaucomatous optic neuropathy unlikely. The absence of pain with eye movement or central scotoma made a diagnosis of demyelinating optic neuritis unlikely. The lack of decreased visual acuity, optic nerve hemorrhages or altitudinal visual field defects made the diagnosis of ischemic optic neuropathy unlikely.
The optic nerve area was greater than 1.4 mm in both eyes, which excluded congenital optic nerve hypoplasia (microdisc). The lack of visual field defects made a diagnosis of stroke or compressive intracranial mass less likely. The patient had no significant risk factors for obstructive sleep apnea such as unhealthy BMI or large neck size. He did complain of sore joints, which could suggest risk for systemic lupus erythematosus or fibromyalgia. There was no evidence of optic nerve elevation or blurred disc margins, which made a diagnosis of optic disc drusen unlikely.
Outcome
The following tests were ordered: SD-OCT of optic RNFL and automated 30-degree visual fields. SD-OCT scans of the optic nerve RNFL in the right eye revealed average thickness of 87 microns. In addition, quadrants superiorly and inferiorly had abnormally thin RNFL measurements. SD-OCT scans of the optic nerve RNFL in the left eye revealed average thickness of 90 microns. In addition, the temporal quadrants had abnormally thin RNFL measurements.
The pattern of GCC thinning was diffuse and crossed the horizontal raphae. The abnormal GCC measurement was symmetric in both eyes, at 81 microns. This may indicate a macular nerve fiber layer defect. For this reason, automated visual fields were obtained. The results were normal and reliable visual field sensitivity in both eyes with no focal scotomas. The mean sensitivity level was lower in the left eye (24.0 dB) compared to the right eye (26.4 dB).
Our patient was referred to his primary care physician (PCP) with a diagnosis of mild nonspecific bilateral optic neuropathy. A written report to his PCP advised that because abnormal optic nerve SD-OCT results can be a biomarker of neurodegenerative disease affecting post-chiasmal visual pathways, a comprehensive physical exam and bloodwork were recommended. Previously, a written report had been sent to the PCP to advise that the patient’s bilateral episcleritis could be a biomarker of systemic inflammatory disease. A request was made to the PCP to report back any positive findings to allow correlation to visual system findings. All of this information was reviewed with the patient.
The patient was fit with new contact lenses. Discussion included the importance of proper contact lens-related hygiene and compliance with prescribed wearing schedule. He was warned that extended wear of contact lenses would increase risk of sight-threatening ulcerative keratitis. The patient was advised to contact the office if he experienced any significant pain, redness or loss of vision. The next scheduled visit in 6 months would include automated visual field testing along with optic nerve SD-OCT imaging of the RNFL and macular GCC to monitor for signs of progressive optic neuropathy.
Spectral-domain OCT (SD-OCT) is a quick, sensitive, non-invasive technology that provides high-resolution measurements of the optic nerve peripapillary retinal nerve fiber layer (RNFL) and the macular ganglion cell complex (GCC). SD-OCT testing of these structures is considered a powerful biomarker of neurodegeneration by allowing us to search for axonal-neuronal integrity in the afferent visual pathway. Notably, there has been evidence of retinal thinning in patients with retrogeniculate lesions that suggests transynaptic retrograde optic degeneration is possible.
Importance of advanced diagnostics
The incorporation of the SD-OCT macular GCC scan may provide additional information in clinical situations that limit the uses of the SD-OCT RNFL scan by itself, such as in presence of optic disc edema or large peripapillary retinal vessels. The retinal ganglion cells are densest in the macula and form a stratified multicellular layer within the central 6 degrees of visual field. Therefore, loss of axons and the corresponding soma in this location is likely to cause a thinning of the retinal ganglion cell layer. In certain cases, macular GCC thickness has been shown to correlate better with visual dysfunction than RNFL thickness.
Although a neurological diagnosis exclusively based on SD-OCT is not possible, it provides a valuable tool for quantifying and tracking neuro-ophthalmic disease progression. Emerging evidence over the past decade indicates that ganglion cell loss is consistent with some descending optic atrophies such as multiple sclerosis. Additional recent data point to ganglion cell loss as a potential sentinel for chronic neurodegenerative diseases such as Alzheimer’s, ALS and Parkinson’s. Definitive protocols and norms have yet to be established for the role of SD-OCT and similar retinal scanning devices. While a definitive diagnosis could not be made from interpreting the current clinical findings, prospective surveillance becomes the management choice.
Our 58-year-old patient presented with signs of symmetric segmental bilateral optic atrophy based on macular SD-OCT screening images. Visual function tests of acuity, automated visual field and color vision were all normal. Structural analysis of optic nerve with SD-OCT showed mild signs of abnormalities. There were no obvious signs of ocular disease to explain these findings. While the findings may have been due to an undiagnosed neurodegenerative condition, they could also have been an artifact from an old infectious or inflammatory process. There may have been early functional vision changes that current technology was not able to detect.
Our patient did not comply with our medical advice and as of this writing had not scheduled a follow up visit with his PCP. Consequently, we were unable to exclude some of the various systemic conditions that are known to cause similar presentations. In cases like this, the answer to the question of “What’s your diagnosis?” may just be: “We do not know yet.”
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- For more information:
- Nicholas Belill, OD, owns a private solo practice in Clio, Mich. He can be reached at lookatsign@gmail.com.
- Leo P. Semes, OD, FAAO, is a Primary Care Optometry News Editorial Board member. He can be reached at leopsemes@gmail.com.
Disclosures: Belill and Semes report no relevant financial disclosures.