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Contradictory test results make diagnosis challenging
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A 32-year-old female was referred to the clinic for confirmation of glaucoma vs. physiologic cupping through electrodiagnostic testing.
A previous diagnosis of glaucoma was made 4 years prior and treated with Travatan Z (travoprost ophthalmic solution 0.004%, Alcon) drops, one drop in each eye once a day. The patient self-discontinued the drops 5 months before presentation due to perceived lack of efficacy and cosmetic hyperemia, which affected her job as a realtor.
Her medical history is largely unremarkable with the exception of essential thrombocythemia, for which she was not receiving treatment, and low blood pressure. Per the patient, her average blood pressure was approximately 100/70 mm Hg. Blood pressure on today’s visit was 118/78 mm Hg. No family history of glaucoma was reported by the patient.
IOP measurements were within the statistically normal range on previous visits over the past 9 months. Preliminary IOP readings upon presentation 5 months post-medication discontinuation were 13 mm Hg OD and OS, taken at 9 a.m. Her best spectacle-corrected vision was 20/25+ OD and OS and 20/20 with both eyes open in the distance. All entrance skills were normal. Her refractive correction was -3.00 D -1.25 D x 145 OD with a -4.75 sphere OS.
Pachymetry readings showed a central corneal thickness of 535 µm OD and 530 µm OS. A fundus exam showed the cup-to-disc ratio was approximately 0.8 mm horizontally and vertically in the right eye and 0.85 mm horizontally and 0.85 vertically in the left eye, indicating a suspicion for glaucoma despite her age. Her disc size was slightly above average size. An A-scan was performed, and her axial lengths were 24.5 mm in both eyes.
The OCT illustrated significant abnormalities with thinning of the retinal nerve fiber layer (RNFL) and ganglion cell complex. The RNFL results were outside the 95% reference range, both inferior and superior in both eyes, with overall RNFL thickness significantly outside the normal ranges for overall analysis, as well as sector and quadrant analysis.
A reliable visual field was obtained in both eyes, with normal results seen in mean deviation and pattern standard deviation. The glaucoma hemi-field test was within normal in both eyes, with no obvious glaucomatous defects seen in either eye.
Initial structural and functional testing provided conflicting data: visual field and IOP appeared to be in normal ranges, while cup-to-disc ratios and RNFL fell outside of clinically normal expectations. Because we had conflicting data, we moved to electrodiagnostic testing and used pattern electroretinography (PERG) to drill down to a definitive diagnosis. PERG responses have been found to be capable of predictive potential for development or progression of glaucoma, or both. The PERG test found no abnormalities, with normal functionality of the ganglion cells in both eyes.
Differential diagnoses
Differential diagnoses for this case include primary open angle glaucoma (POAG), normal tension glaucoma (NTG), glaucoma suspicion and physiologic cupping. We did not feel that descending optic atrophy should be included.
While POAG is often associated with elevated IOPs, this patient’s consistently low IOP does not rule out the possibility of the disease. Several population-based studies (Wilsey et al., Ventura et al., Leal-Fonseca et al., Ma et al.) have shown that a number of patients can suffer from glaucoma without expected elevated pressures. Abnormal cupping could indicate the presence of NTG. There is also speculation that low blood pressure may contribute to NTG. If this is the case, glaucoma could be triggered at a lower-than-average IOP, as this patient’s pressure naturally runs lower.
With or without glaucoma, it is possible that this patient’s abnormally low blood pressure is a key factor in her symptoms and testing results. While high blood pressure is typically seen as “bad,” an abnormally low blood pressure is also concerning. Sufficient blood pressure is necessary to perfuse organs with needed blood, nutrients and oxygen, and without that pressure, organs may suffer. With this patient’s pressure already low, any nocturnal dips could cause insufficient blood flow to the optic nerve. While no sleep study was ordered, the patient commented that her typical blood pressure is 98/68 mm Hg, so we speculated that there could be a connection there.
Physiologic cupping is likely, as indicated by “red disease” on the OCT. Red disease refers to a result being present in only 1% of the reference database. This causes the instrumentation to indicate disease when disease is not truly present. To avoid under or over treating a patient, it is critical to understand the parameters of the diagnostic tools being used. OCTs provide a great deal of information, and incorrect interpretation of that data could lead to misdiagnosis.
Research suggests that 15% to 36% of OCTs result in a false positive (Leal-Fonseca et al.). An OCT scan with data falling outside the ranges of the normative database may seem to indicate that disease is present; however, all this truly illustrates is that a particular index falls outside a particular parameter. It is not a true indication of whether or not disease is present. Overall, normal for RNFL is between 85 m and 105 m. Our patient had RNFL of 64 m in her right eye and 65 m in her left eye. While this is abnormally thin, care should be taken when interpreting information, and results should be corroborated.
Diagnosis, treatment
The positive or normal functionality shown with the visual fields and PERG testing seems to indicate an absence of disease in this patient. It confirms the relatively shallow cupping of the ONH, as is seen in the cross section on OCT and is consistent with the normal visual fields. In our minds, if the structural deficits on the OCT are truly present, indicating significant disease of the RNFL and ganglion cells, how could the two functional tests be perfectly normal?
With no other data available, our diagnosis is congenital physiologic cupping at this point due to the OCT readings, normal functional testing and the nonpathologic nature of the cupping. The patient is not being treated at this time although she will be closely monitored. Also factoring into our decision was the fact that the patient self-discontinued her eye drop therapy recently, and her IOPs did not significantly increase without the drops. Even if we prescribed therapy today, would she take the drops? Would we get much IOP reduction when her IOP was already 13 mm Hg? She will return in approximately 4 to 6 months for a pressure recheck and repeat visual fields and PERG testing.
- References:
- Leal-Fonseca M, et al. Graefes Arch Clin Exp Ophthalmol. 2014;doi:10.1007/s00417-013-2529-7.
- Ma X, et al. Med Sci Monit. 2016;doi:10.12659/MSM.898564.
- Wilsey LJ, et al. Curr Opin Ophthalmol. 2016;doi:10.1097/ICU.0000000000000241.
- Ventura LM, et al. Ophthalmology. 2005;doi:10.1016/j.ophtha.2004.07.018.
- For more information:
- Nate R. Lighthizer, OD, FAAO, is the assistant dean of clinical care services at Northeastern State University in Tahlequah, Okla., and a member of the Primary Care Optometry News Editorial Board. He can be reached at: lighthiz@nsuok.edu.
Disclosure:Lighthizer reports he is on the advisory board for Aerie Pharmaceuticals, Alcon and Nova Oculus and receives speaker honoraria from BioTissue, Diopsys, Nidek, Optovue, Quantel, Revolution EHR and Shire.