Ophthalmologic Manifestations of Multiple Sclerosis 

Common neuro-ophthalmologic manifestations of multiple sclerosis (MS) are unilateral vision loss due to optic neuritis (ON) and oscillopsia due to nystagmus and diplopia (eg, internuclear ophthalmoplegia [INO], ocular motor palsy). Other common neurologic symptoms are sensory disturbances, motor weakness, and trigeminal neuralgia. Patients with ophthalmic symptoms consistent with a possible MS attack should therefore be questioned about historical features that may be suggestive of MS (eg, prior neurologic deficit, prior diplopia or loss of vision, prior neuroimaging studies).

Diplopia may be due to an INO or an ocular motor cranial neuropathy, typically a sixth nerve palsy; third and fourth cranial neuropathies are uncommon in MS. In an INO, an adduction deficit of the ipsilateral eye is present, with horizontal gaze nystagmus in the contralateral abducting eye. The lesion involves the medial longitudinal fasciculus (MLF). The occurrence of bilateral INO is considered to be highly suggestive of MS, especially in young patients.

A new-onset acquired pendular nystagmus is relatively common, but upbeat, downbeat, convergence-retraction, and other forms of nystagmus may occur as well, depending on the location of the demyelinating lesion.

Combinations of deficits may also occur in MS, including the following:

• Horizontal or vertical gaze palsies
• Wall-eyed bilateral INO (WEBINO)
• Wall-eyed monocular INO (WEMINO)
• Paralytic pontine exotropia
• One-and-a-half syndrome

The classic clinical picture of MS is one of multiple neurologic symptoms disseminated in space and time. More specifically, over time, patients manifest episodic neurologic dysfunction due to inflammation in different regions of the central nervous system (CNS).

Special considerations

Patients with ON should be cautioned to avoid work and other activities that may require greater visual skills than they possess. Use of machinery, heavy equipment, or sharp instruments, as well as other visually demanding activities, may have to be avoided until the patient recovers sufficient vision, stereovision, color vision, and contrast acuities.

Patients should know that vigorous physical activity, hot baths, and other activities that raise their core body temperature might result in temporary decreases in vision because of the Uhthoff phenomenon.

Patients with ON, particularly those with abnormal findings on magnetic resonance imaging (MRI), should be offered the opportunity to consult with a neurologist regarding the possibility of MS. A formal consultation with a neurologist is indicated especially if the referring physician is unable or unwilling to discuss the complex issues surrounding the evaluation, treatment, and prognosis of MS.

Patient education

The association of MS with ON is a delicate subject that requires extensive patient education, reassurance, instruction, and counseling. Patients, especially those in higher-risk populations, should be informed of the relationship between specific monosymptomatic ophthalmologic events (eg, internuclear ophthalmoplegia), ON, and MS. Patients should be reassured that most people with ON improve regardless of treatment. For patient education information, see the Brain and Nervous System Center, as well as Multiple Sclerosis.

Approximately 20% of patients with MS present with optic neuritis (ON) as the first demyelinating event, whereas 40% of patients may present with ON during the course of their disease. Pathologic studies have demonstrated that subclinical optic nerve involvement is very common among patients with MS, and the percentage of patients with anterior visual axis involvement from the disease is likely much higher.^[1] Therefore, diagnosing ON is potentially an important step in providing appropriate therapy for the patient; however, not everyone who develops ON develops MS.

ON typically causes acute to subacute unilateral loss of visual acuity (which may progress over days to weeks), color and contrast sensitivity, and visual field changes. Most patients with ON develop retrobulbar pain that is worse with extraocular movement. The loss of visual acuity in patients with ON may range from minimal to profound.

Patients with ON may describe phosphenes or transient flashes of light or black squares lasting from hours to months. Either movement or sound may induce them. They may occur before or during an ON event or even several months following recovery. Although visual acuity typically recovers after ON, patients may continue to complain of residual deficits in color, contrast sensitivity, brightness, and stereovision.

Visual field changes are common in patients with ON and are typically nerve fiber layer defects. The classic visual field defect of ON is the central scotoma, but any nerve fiber type defect may occur. Patients with ON typically have loss of visual acuity and visual field in the ipsilateral eye. Contralateral and often asymptomatic visual field loss may also be detected. A relative afferent pupillary defect is present in unilateral cases and in bilateral, but asymmetrical, cases, but the relative afferent pupillary defect may be absent in bilateral, symmetrical cases.

Although most adult patients with demyelinating ON have retrobulbar neuritis, the disc may show mild hyperemia. Severe disc edema, marked hemorrhages, or exudate should prompt reconsideration of a diagnosis of demyelinating ON. Most cases of ON are retrobulbar. In these cases, "the patient sees nothing, and the doctor sees nothing" (ie, the fundus is normal). Optic disc pallor, sector or diffuse, often follows either anterior ON or posterior ON.

Other fundus findings, including anterior uveitis, vitreitis, vascular sheathing, and disc and papillary hemorrhages, as well as compromise of the central arterial and venous circulations, are uncommon. The amount of inflammation, the changes in visual field, and the loss of visual acuity do not correlate directly with the appearance of the disc.

Other reported visual changes in patients with ON include decreased visual acuity in bright light (about 50% of patients see better in dim light rather than in bright light), flickering scotomata, and the Uhthoff phenomenon. The Uhthoff phenomenon is an exacerbation of the patient's symptoms when exercising or when exposed to temperature change. The most notable symptoms affected by the Uhthoff phenomenon are transient visual obscurations, dyschromatopsia, and contrast sensitivity changes. The symptoms tend to resolve with restoration of euthermic conditions. Most symptoms of the Uhthoff phenomenon resolve from within 60 minutes to 24 hours.

In the Optic Neuritis Treatment Trial (ONTT), mild to severe pain was present in 92.2% of patients.^[2] Pain was constant in 7.3% of patients, constant and worse on extraocular motility in 51.3% of patients, and noted only with eye movement in 35.8% of patients.

Providers should be alert to the potential for the misdiagnosis of ON and its attendant legal ramifications, wherein a patient presents with atypical features (eg, older age, progression rather than recovery, marked hemorrhages or exudates) and the physician fails to perform neuroimaging studies, especially when atypical symptoms (eg, painful, acute retrobulbar visual loss with bitemporal hemianopsia in pituitary apoplexy) are exhibited.

The Optic Neuritis Treatment Trial (ONTT) was designed to compare the speed and level of visual recovery between patients treated with oral prednisone, intravenous methylprednisolone (IVMP), or placebo. Patients were randomized into 1 of 3 groups within 8 days of symptom onset. Those treated with oral prednisone (1mg/kg/day for 14 days) demonstrated an increased incidence of recurrent ON compared with those treated with IVMP (250mg every 6h for 3 days, followed by an oral taper) or placebo.^[2]

The ONTT results suggest that IV steroids, oral steroids, and placebo all result in recovery of visual function over time. IV steroids hasten the rate of recovery but do not change the final visual outcome. In the ONTT, IV steroids seemed to decrease the incidence of the development of MS over a 2-year period, but this effect was not sustained after year 3.

At entry into the ONTT, 35% of patients had a visual acuity of 20/40 or better, 30% of patients had a visual acuity of between 20/50 and 20/200, and 35% of patients had a visual acuity of 20/200 or worse. Only 3% of patients had no light perception (NLP). Therefore, NLP should be considered a red flag for a diagnosis of ON; in such cases, other potential etiologies for vision loss (eg, inflammatory, infiltrative, neoplastic) may need to be considered.

Nearly 100% of patients in the trial whose visual acuity was 20/50 or worse had a defect in their color sensitivity, and in those patients with a visual acuity of 20/20 or better, 51-70% had altered color vision.

Seventy-four percent of patients in the ONTT recovered visual acuity of 20/60 or better by 8 weeks, and most patients had a visual acuity of better than 20/40 by 6 months.

The most common visual field defects were as follows, in decreasing order of frequency:

• Altitudinal - 28.8%
• 3 quadrant - 14.0%
• 1 quadrant - 11.8%
• Centrocecal - 8.7%
• Hemianopic - 8.3%
• Peripheral rim - 7.0%
• Arcuate - 7.4%
• Central - 7.0%
• Enlarged blind spot - 2.6%
• Nasal step - 1.3%

Mild to severe pain was present in 92.2% of patients.^[2] Pain was constant in 7.3% of patients, constant and worse on extraocular motility in 51.3% of patients, and noted only with eye movement in 35.8% of patients.

Although all 3 treatment arms of the study had equal visual outcomes, oral prednisone in conventional doses increased the likelihood for a recurrent episode of ON and is not recommended. Higher doses of oral methylprednisolone have not produced similar increased recurrence rates of ON, but the number of patients in these studies was small.

Laboratory studies were not deemed helpful in establishing a typical demyelinating ON diagnosis (ie, acute, unilateral optic neuropathy in a young patient with pain on extraocular movement and improvement over time). A lumbar puncture was optional and showed evidence of demyelinating disease only in patients with ON.^[2]

Risk of developing MS

Among patients who had no lesions on their baseline MRI scan, male gender and optic disc swelling were associated with a lower risk of MS, as were the following features:

• NLP vision
• Lack of pain
• Fundus findings of severe optic disc edema, peripapillary hemorrhage, or retinal exudates

The strongest predictor for future development of MS was the presence of white matter lesions on an MRI; this risk was increased with the presence of spinal lesions.

Five years after the original ONTT, 16% of patients with no plaques on the baseline MRI developed MS.^[3] Forty percent of patients with 1 or 2 high-signal densities developed MS, and, of those with more than 2 lesions, 51% developed clinically definite MS (CDMS) over the same period of time. After 10 years of follow-up, after the ONTT, patients who had 1 or more lesions on the baseline MRI had a 56% risk of CDMS, and those patients with no lesions had a 22% risk of future development of MS.

Follow-up data from the ONTT revealed that the cumulative probability of developing MS within 15 years after ON onset was 50% and was strongly related to the presence of lesions on a baseline non–contrast-enhanced MRI of the brain.^[4] Twenty-five percent of patients with no lesions on baseline brain MRI developed MS during follow-up, compared with 72% of patients with 1 or more lesions.^[3]

At the time of follow-up, most patients had near normal visual acuity, even if they had a recurrent episode of ON. The investigators found that 87% of patients had a visual acuity of 20/25 or better, 7% had a visual acuity of between 20/25 and 20/40, and 6% had a visual acuity that was worse than 20/50. Of that last group (6%), one half had a visual acuity of 20/200 or worse. Findings from the ONTT showed that the visual acuity results obtained did not statistically differ by the type of treatment the patient received but that the rate of recovery did.^[3]

In the Optic Neuritis Treatment Trial (ONTT), laboratory studies were not deemed helpful in establishing a typical demyelinating ON diagnosis (ie, acute, unilateral optic neuropathy in a young patient with pain on extraocular movement and improvement over time).^[2] However, laboratory studies can be helpful in patients with features that are atypical for demyelinating optic neuritis (ON). These studies, which should be performed as a directed evaluation based on the history and physical examination findings, should include the following:

• Complete blood count (CBC)
• Serum vitamin B-12 and folate levels - Eg, bilateral central scotoma
• Lyme titers - Eg, endemic area, tick exposure, rash
• Tuberculin (TB) skin test - Eg, tuberculosis (TB) exposure, endemic area
• Fluorescent treponemal antibody (FTA) test - Eg, syphilis
• Venereal Disease Research Laboratories (VDRL) test or rapid plasma reagin (RPR) test - Eg, syphilis
• Antinuclear antibody - Eg, systemic lupus erythematosus
• Human immunodeficiency virus (HIV) - Eg, high-risk patients
• Angiotensin-converting enzyme (ACE) level - Eg, sarcoidosis
• Erythrocyte sedimentation rate - Eg, inflammatory disorders
• Serum neuromyelitis optica (NMO) antibody immunoglobulin-G (anti – aquaporin-4 [AQP4] antibody) testing

Although some interest has been shown in human leukocyte antigen (HLA) typing in ON (eg, HLA-DR2, HLA-B7, HLA-Dr4, HLA-Dw2), the clinical use of these tests remains unproven.

According to Polman and colleagues, the McDonald criteria, which were intended to aid in the diagnostic evaluation of MS by incorporating MRI findings into the evaluation and diagnosis of the disease, have been extensively assessed and used since 2001. The 2005 revisions helped to simplify and speed diagnosis while maintaining adequate sensitivity and specificity. The International Panel on the Diagnosis of MS put forth the McDonald criteria, named after Dr. Ian McDonald, who chaired the panel.^[5]

Typical cases of optic neuritis (ON) do not warrant extensive investigations. Advances in MRI techniques, however, have improved the ability to visualize damage to the anterior visual axis. MRI is superior to computed tomography (CT) scanning in examinations related to MS. Although secondary causes of ON, including neoplastic changes, granulomatous lesions, neuropathies, and other inflammatory conditions, may be seen on a cranial MRI, the major rationale for performing a cranial MRI is to evaluate demyelinating lesions and to identify the future risk of MS.

The presence of asymptomatic white matter lesions on MRI is the most potent predictor that MS will develop.^[6] Although a high number of white matter lesions present on a cranial MRI are more suggestive of MS, even 1 white matter lesion may be significant. On the other hand, a normal MRI at onset lessens the chance for future development of MS but does not exclude the possibility.

The lesions on an MRI are typically bright on T2-weighted imaging (see the image below) and can be highlighted by suppressing the normal cerebrospinal fluid signal using fluid-attenuated inversion recovery (FLAIR). MS plaques are usually periventricular, ovoid in shape, large, and multiple. Involvement of the corpus callosum is particularly suggestive of demyelinating disease. Active MS plaques may show enhancement after gadolinium administration.

Optical coherence tomography scanning

Advances in ocular imaging with optical coherence tomography (OCT) scanning have made it possible to quantify, in vivo, retinal nerve fiber layer atrophy in patients with MS as a structural marker of axonal injury in the afferent visual pathway. Studies have shown that OCT-measured retinal nerve fiber layer (RNFL) values are reduced in patients with MS with and without a history of optic neuritis (ON). However, RNFL atrophy tends to be greater in ON-affected eyes.^{[7, 8]}

Visual evoked potentials

Visual evoked potentials (VEPs) are not typically necessary for patients with clear clinical evidence of ON. However, VEPs may be a valuable means of assessing any subclinical fellow eye involvement.

Lumbar puncture

In the Optic Neuritis Treatment Trial (ONTT), a lumbar puncture was optional and only showed evidence of demyelinating disease in patients with ON.^[2] The cerebrospinal fluid may be useful for diagnostic purposes in atypical cases of ON or in patients in whom a diagnosis of MS requires support from additional paraclinical evidence (eg, elevated immunoglobulin-G synthesis, oligoclonal bands).

The most common form of optic neuritis (ON) is a unilateral, idiopathic, inflammatory, demyelinative process involving neutrophils, lymphocytes, plasma cells, and macrophages, occurring either anterior or posterior to the lamina cribrosa. Although demyelination is a process that causes a mostly mononuclear infiltration of the perivascular spaces, initial examination of the axons may show no structural changes until the disease has progressed.

Once the disease has progressed, inflammatory and cellular responses cause the breakdown of myelin into fat globules, thereby altering the structure of the nerve. Ingestion of fat droplets by macrophages causes the stimulation of astrocytes and the formation of glial tissue visualized as plaques on an MRI scan. This process is responsible for damaging neurons and increasing the latency and transmission times along the axons. This process is also responsible for the formation of plaques visualized on T2-weighted imaging.

Thus, the pathologic findings in MS include inflammation, demyelination, and axonal loss. The degree of axonal loss may explain the lack of a complete recovery of function in patients with MS, especially after repeated attacks.

Optic neuritis (ON) is generally an idiopathic or demyelinating process. Although the most important association of ON is that with MS, other conditions can produce an optic neuropathy, including the following:

• Inflammatory - Eg, sarcoidosis, systemic lupus erythematosus, polyarteritis nodosa, Wegener granulomatosis
• Infectious - Eg, spirochetes, Lyme disease, syphilis, hepatitis B, varicella zoster, HIV, Epstein-Barr virus, cytomegalovirus, mycobacteria, fungi
• Infiltrative processes - Eg, leukemia, lymphoma
• Toxins - Eg, antimetabolites, phenothiazines, isoniazid, ethambutol
• Nutritional deficiencies - Eg, vitamin B-12, folate
• Compressive lesions - Eg, tumor, aneurysm, thyroid orbitopathy
• Ischemic optic neuropathy - Eg, anterior ischemic optic neuropathy, posterior ischemic optic neuropathy, antiphospholipid antibody syndrome

AION

The major differential diagnoses in a case of unilateral and acute optic neuropathy with optic disc edema include ON and ischemic optic neuropathy. Typically, a younger patient has ON and an older patient has anterior ischemic optic neuropathy (AION). Although the visual loss is sudden in ON and AION, pain is less likely to occur in AION, and only mild to moderate visual improvement occurs after AION. The disc swelling in AION is typically more severe than in ON, and associated hemorrhages and exudates are features that argue against demyelinating ON.

Leukemia and lymphoma

Leukemic infiltration and lymphomatous lesions may create symptoms and a disc appearance similar to that of ON. If a history of such a disorder is noted, ruling out either a progression or a relapse of the lymphoproliferative condition is essential. An infiltrate that is visible on the disc head itself is often a clue regarding the underlying etiology.

Inflammatory disorders

Sarcoidosis, lupus, and other autoimmune disorders can produce an inflammatory optic neuropathy. The presence of associated anterior or posterior uveitis, a steroid-dependent course or markedly steroid-responsive course, and a history of systemic inflammatory disease are helpful in differentiating these conditions from ON. MRI is helpful in these cases.

Compression

Although thyroid ophthalmopathy (Graves ophthalmopathy) may produce a compressive optic neuropathy, a gradual, rather than an acute, decrease in visual acuity typically occurs. Usually, the patient has a history of autoimmune thyroid disease and signs of thyroid orbitopathy (eg, upper lid retraction, lid lag, ophthalmoplegia, proptosis). Orbital imaging differentiates compressive optic neuropathy from Graves disease and from optic neuritis.

Intraorbital/intracranial compressive lesions typically produce painless, progressive, compressive optic neuropathy (eg, optic nerve sheath and intracranial meningiomas, sellar lesions).

Toxins

Certain toxins and medications (eg, tobacco, ethanol, methanol, ethambutol, isoniazid, chloroquine, some antineoplastic agents) can produce an optic neuropathy. Typically, patients in these cases have a bilateral and simultaneous central or cecocentral loss.

Other

Leber hereditary optic neuropathy is a painless, progressive, and typically bilateral optic neuropathy that produces a central or cecocentral scotoma. The disorder is mitochondrially inherited and primarily affects young men.

Neuromyelitis optica (NMO) is a severe inflammatory process of the optic nerves that is often associated with poor clinical recovery. In addition to optic nerve involvement, typical features of NMO include episodic myelitis (with spinal lesions that extend 3 or more spinal segments), an absence of clinical manifestations of brain involvement, and an absence of brain MRI lesions. Lennon and colleagues described a putative marker for NMO; ie, NMO-immunoglobulin G, an autoantibody that binds at or near the blood-brain barrier and distinguishes NMO from MS.^[9]

In the Optic Neuritis Treatment Trial (ONTT), patients treated with oral prednisone (1mg/kg/day for 14 days) demonstrated an increased incidence of recurrent optic neuritis (ON) compared with those treated with intravenous methylprednisolone (IVMP) (250mg every 6h for 3 days, followed by an oral taper) or placebo.^[5]

Although all 3 treatment arms of the study had equal visual outcomes, oral prednisone in conventional doses increased the likelihood for a recurrent episode of ON and is therefore not recommended. Higher doses of oral methylprednisolone have not produced similar increased recurrence rates of ON, but the number of patients in these studies was small.

The ONTT results suggest that IV steroids, oral steroids, and placebo all result in recovery of visual function over time. IV steroids hasten the rate of recovery but do not change the final visual outcome. In the ONTT, IV steroids seemed to decrease the incidence of the development of multiple sclerosis (MS) over a 2-year period, but this effect was not sustained after year 3.

Newer studies have supported the benefit of using immunomodulatory agents (eg, interferon beta-1) in the reduction of clinically definite MS (CDMS). The role of disease-modifying agents in the treatment of ON is not to expedite the recovery of optic nerve function, which tends to be good, but rather to reduce the risk of future MS.

Three studies have addressed the role of interferon therapy for acute monosymptomatic ON and the future development of CDMS^[10] :

• The Controlled High Risk Subjects Avonex Multiple Sclerosis Prevention Study (CHAMPS)^{[11, 12]}
• The Early Treatment of Multiple Sclerosis (ETOMS) trial^[13]
• The Betaseron/Betaferon in Newly Emerging Multiple Sclerosis for Initial Treatment (BENEFIT) trial^[14]

CHAMPS demonstrated a significantly lower rate (44%) of development of CDMS among the patients in the treatment group and a relative reduction of new lesions in the cranial MRI among patients treated with interferon versus the placebo group. In CHAMPS, patients with a single, clinically isolated neurologic event (ie, ON, brainstem or cerebellar syndrome, incomplete transverse myelitis) were enrolled into a randomized, placebo-controlled trial if they had 2 or more clinically silent lesions on a cranial MRI.^{[11, 12]} After initial treatment with high-dose IVMP, half the patients received weekly interferon beta-1a (30mcg once per week), and half the patients received placebo. The primary endpoint was the development of CDMS, and the secondary endpoint was the brain MRI.

In ETOMS, 45% of the placebo group developed CDMS after 2 years, compared with 34% of the patients given subcutaneous interferon beta-1a (22mcg once per week). During the treatment study period, the MRI activity and burden of disease measured by MRI were significantly reduced in the treatment group. ETOMS enrolled patients with 4 asymptomatic white matter lesions (or 3 lesions if one enhanced with gadolinium) present on the cranial MRI at presentation. Half the patients received subcutaneous interferon beta-1a, and half the patients received placebo. After 2 years, the odds ratio for the development of CDMS was 0.61 in the treatment group versus the control group.

In the BENEFIT trial, interferon beta-1b (250mcg subcutaneously on alternate days) delayed the time to diagnosis of MS by clinical and McDonald criteria. The trial looked at the role of disease-modifying therapy in patients with clinically isolated syndromes (either monofocal or multifocal) and at least 2 clinically silent brain MRI lesions. Subjects were randomized to receive interferon beta-1b or placebo until CDMS was diagnosed or the study period of 24 months was reached.

Although corticosteroids are known to have multiple short-term and long-term adverse effects, in general, a day course of IVMP followed by an oral taper over 10-14 days does not produce significant or permanent adverse effects in otherwise healthy young patients.

Methylprednisolone, prednisone taper, and interferon-beta therapy can be administered either at home or in a hospital setting. The location of care should be determined by the severity of the patient's condition, as well as by the patient's ability to comply with prescribed health care, present financial status, and other coexisting medical and psychological issues.

The risk of developing MS after optic neuritis (ON), as calculated in various studies, differs according to the length of follow-up in the individual investigation, with higher MS estimates occurring in studies with longer-term follow-up. An abnormal baseline MRI finding is the strongest predictor of future development of MS.

According to data from the Optic Neuritis Treatment Trial (ONTT), the cumulative probability of developing MS by 15 years after the onset of ON is 50% and is strongly related to presence of lesions on a baseline MRI scan of the brain.^[4] In the ONTT, 25% of patients with no lesions on baseline brain MRI developed MS during follow-up, compared with 72% of patients with 1 or more lesions.^[3]

Disability from MS has been reported to be less likely in patients who present with ON as their first demyelinating event, few or no MRI lesions, a long period to first relapse, and no disability after the first 5 years of diagnosis. Nevertheless, neither the presence nor the absence of signal abnormalities on the MRI is 100% predictive of whether a patient will develop MS.

The size and the location of ON enhancement may be of prognostic significance in ON. Miller et al reported that lesions greater than 1cm in length or located within the optic canal were associated with a decreased rate and quality of visual recovery.^[15] Dunker and Wiegand also reported incomplete recovery in lesions greater than 17.5mm in length and/or located intracanalicularly.^[16]

Other predictive factors include the following:

• Prior history of ON
• Early recurrence of ON
• Early age of onset
• Positive family history of MS
• Human leukocyte antigen (HLA)-DR2 tissue haplotype
• Northern European ancestry

Abnormalities in the cerebrospinal fluid, such as immunoglobulin G and oligoclonal bands, may be predictive of the development of MS.

Male patients who have no light perception (NLP) vision, experience no pain, or have an atypical optic disc appearance (eg, hemorrhages, marked swelling) are less likely to develop MS.

Various aspects of vision have been found to recover differently following resolution of acute ON. One study followed individuals who experienced ON either in 1 eye or simultaneously in both eyes and then recovered a vision acuity of 20/30 or better at 6 months. In this study, 85% of 27 patients noted some improved change in the quality of their vision. Objectively, relative afferent pupillary defects (89%) were determined to be the most commonly retained defects, followed by persistent decreased brightness (89%) and altered stereo acuity (80%). Following these changes were disc pallor (77%), depressed contrast sensitivity (72%), dyschromatopsia (57%), and perimetry defects (26%).