Systemic Disease and Optometry
Systemic Disease and Optometry
Improve patient care — and referrals — with a focus on detecting four common systemic diseases.
WILLIAM MARCOLINI, O.D., F.A.A.O., Iselin, N.J
I'LL NEVER FORGET THAT DAY IN 1999. As a student at the Pennsylvania College of Optometry, I mentioned to two practicing optometrists that my passion was ocular disease. "OCULAR DISEASE!" they exhorted. "Disease is great, but that's not how you'll make a living!" Downtrodden, I trudged back to class with my tail between my legs.
A decade of practice has taught me that they were basically right. However, while we do earn the majority of our income from the optical, we are uniquely positioned, as primary eyecare providers, to identify systemic disease as well. Specifically, as our access to medical insurance plans increases, patients recognize our special role in treating not only their eyes, but also contributing to their overall wellbeing.
So the passion lives on, and as primary-care optometrists, we must be comfortable in managing or co-managing patients. Detect a systemic disease in your patient, and that patient is grateful for a lifetime — and the source of endless of referrals, as they never fail to mention: "Guess what my eye doctor found?"
A case in point
During an office visit several years ago, a patient handed me his glasses and exclaimed, "I don't need these anymore." Upon examination, his unaided acuity was 20/25 OD and 20/30 OS. When he wore his habitual prescription, his vision dropped to 20/80 OU!
The change in refraction was:
OD: +1.75 −1.00 x 060 20/80
OS: +1.75 −1.00 x 124 20/80
+0.25 −0.75 x 060 20/20
−0.25 −0.50 x 100 20/20
He thanked me and wanted me to congratulate him on his "natural LASIK."
My initial thought was that he was experiencing a myopic shift due to increased nuclear sclerosis, yet a dilated fundus examination showed symmetric trace nuclear changes, which were consistent with the results of his last exam from only six months earlier. A more detailed history was in order.
During our interview, the patient acknowledged that he woke up four times a night to urinate. In addition, he said that he had lost weight, even though it was the holiday season. I instructed the patient to make an appointment with his primary-care physician (PCP) immediately. At his visit to the PCP, tests revealed the patient had a blood sugar reading of 430 mg/dL. As a result, his physician diagnosed him with type 2 diabetes.
While the number of systemic conditions that affect the eye is staggering, it is worthwhile to focus on those you may see everyday. Here, I will discuss four of the more common conditions: diabetes mellitus, systemic hypertension and hypercholesterolemia, neurological disease and systemic inflammatory disease.
Diabetes can affect the clarity of the lens, its refractive index and the patient's measured accommodative amplitude. As the glucose levels in the aqueous rise, so do the glucose levels in the lens. This causes aldose reductase to convert glucose to sorbitol, which is not metabolized, but rather remains in the lens. Water follows, and the result is swollen lens fibers.
Diabetic patients often manifest transient refractive changes, mostly of the myopic variety, but occasionally hyperopic shifts have been observed.1 Of interest, patients who have diabetes typically show decreased amplitudes of accommodation, and presbyopia may present at an earlier age.1
Other research has hypothesized that changes in the flat meridian of the cornea — rather than biochemical changes in the lens — may be the culprit in refractive changes, and that when glycemic control is restored, there is a shift in the hyperopic direction.2 This is significant in that you can reassure your patients that the changes in their prescriptions are temporary. Once patients achieve glycemic control, their refractive errors should return to previous levels. Consequently, advise those who experience diabetic vision changes and have scheduled refractive or cataract surgery to postpone surgery until their glucose levels stabilize.
The American Diabetes Association has revised its clinical practice recommendations for diabetes diagnosis. The PCP should perform a hemoglobin A1C test. Long associated with monitoring the glucose levels of those with confirmed diabetes, the hemoglobin A1C is considered a fast, easy test to diagnose pre-diabetes.3
For your part, complete a comprehensive exam with pupillary dilation to look for the posterior segment features common in diabetics, such as micro-aneurysms, dot and blot hemorrhages, lipid exudates, clinically significant macular edema (CSME), cotton-wool spots and neovascularization (signs of capillary nonperfusion). Referral to a retinologist is warranted with signs of CSME, proliferative diabetic retinopathy, and/or when the patient has reduced visual acuity of an undetermined cause. (See "Diabetic Retinopathy: Risk Grows With Time".)
Diabetic Retinopathy: Risk Grows With TimeThe longer a patient has diabetes, the greater the chance of retinopathy. In fact, after 10 years of either Type I or Type II diabetes, 67% to 89% of patients have diabetic retinopathy.4 Though panretinal photocoagulation, grid laser and vitrectomy remain the mainstays of treatment, new technologies offer hope. These new therapies may be beneficial in the treatment of diabetic retinopathy and include anti-vascular endothelial growth factor agents (VEGF), corticosteroid injections and antisense oligonucleotide therapies that may potentially target a number of additional diabetic retinopathy-related factors and processes.5
Not only have treatment options expanded, but the manner in which they may be delivered has too. Recently, an extended release intra-vitreal corticosteroid insert for macular edema treatment (Iluvien, Alimera Sciences) showed positive results in phase III trials. It reduced macular edema for up to 36 months.6 The traditional side effects of increased IOP and cataractogenesis with steroid use will have to be monitored closely and may limit the clinical application of this treatment modality.
Systemic hypertension and hypercholesterolemia
It's estimated that 60 million Americans suffer from hypertension, and an estimated 100 million Americans have total cholesterol above 200 mg/dL. Systemic hypertension can lead to hypertensive retinopathy, which can present with mild signs, such as arteriolar-venous crossing changes and flameshaped hemorrhages, or with more serious findings, such as optic nerve edema and choroidal infarcts (Elschnig's spots).
Patients who have increased total cholesterol are at significant risk for arterial disease and have an increased incidence of retinal artery occlusions, both branch and central.
Hypercholesterolemia, hypertension and artherosclerosis are all associated with both coronary artery and carotid artery disease. Often, examination of the retinal arterioles may provide ophthalmoscopic evidence of such disease. Retinal plaques are not uncommon in patients who have diseases of this type. When cholesterol is the source of the plaque in the arterial lumen, it is called a Hollenhorst plaque. Hollenhorst plaques appear as yellow refractile bodies located at a vessel bifurcation and usually arise from carotid atheromas. Other plaques can be cardiac in origin and be calcific or plateletfibrin in nature.
When patients have signs of hypertensive retinopathy, a retinal plaque, an acute branch artery or central retinal artery occlusion (CRAO), refer them to their PCP for a complete systemic work-up. Attention should be directed toward carotid artery evaluation, a lipid profile, blood pressure measurement, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) test and tests for blood clotting abnormalities. (Note that acute CRAO, while uncommon, is a true ocular emergency. In this case, refer the patient immediately to the emergency room for ophthalmological consult, as sight-saving interventions to dislodge the emboli are sometimes employed.)
Often, I think back to my college roommate whose mother suffered from "uveitis," a term I was not familiar with at the time. For years, she suffered from ocular pain and photophobia as she underwent repeated steroid injections, with subsequent pressure spikes. While out to dinner one evening, she felt abnormally out of breath and thought she may be having a heart attack. A chest X-Ray and further blood testing ruled out a myocardial infarction, yet it was discovered that she had advanced, undiagnosed sarcoidosis.
The classic ocular signs of uveitis are well known to optometrists. Proper documentation and grading of cells and flare is essential in monitoring the progress of your patient. A thorough inspection of the anterior and posterior segments of the eye is absolutely crucial in managing patients who have suspected uveitis.
Perform a dilated fundus examination to look for optic nerve edema and retinal vasculitis. For cases of moderate to severe anterior uveitis, frequent topical dosing of steroids q1h and cycloplegia is warranted. Retroseptal Kenalog injections may also be necessary, especially in eyes that are recalcitrant to topical therapy.
Many experts advocate aggressive treatment to prevent sequelae, such as posterior synechiae or peripheral anterior synechiae, since both can potentially lead to uveitic glaucoma and a poor prognosis for the patient. I educate my patients that our number one priority is to eradicate the inflammation and reduce the risk of more serious consequences. Our second priority, then, is to identify any potential underlying systemic disease that may be the cause of the uveitis.
Patients with uveitis and suspected underlying systemic disease should undergo a targeted workup, based upon the patient's demographics and presenting symptoms. A number of tests should be ordered, including:
► a complete blood count (CBC)
► human leukocyte antigen B27 (HLA-B27) test for ankylosing spondylitis, Crohn's disease or Reiter's syndrome
► ESR test for general inflammation
► antinuclear antibody test (ANA) test for lupus, Lyme disease and toxoplasmosis titers
► rapid plasma regain (RPR) test and venereal disease research laboratory (VDRL) test for syphilis
► CRP test and angiotensinconverting enzyme (ACE) test for sarcoidosis
A chest x-ray may also be warranted if the patient presents with symptoms, such as coughing, difficulty breathing or night sweats.
The primary-care optometrist's role in uveitis is treating the ocular findings and identifying potential underlying systemic disease. Appropriate referrals and communication with an ophthalmologist (when injections are required), as well as the patient's PCP, an infectious disease specialist, rheumatologist, etc., may be warranted.
Can an eye that looks perfectly pristine still be a harbinger of a significant systemic disease? Let's say a 28-year-old Caucasian female presents to your office complaining of eye pain and blurred vision, "like someone is shining a bright light into her eye." Sure enough, her acuity in the affected eye is 20/70. Refraction reveals no improvement. Close inspection of the anterior segment is unremarkable, intraocular pressure is normal, dilated fundus examination shows a pink, healthy and intact neural retinal rim.
Yet it's the results of the entrance tests that have you worried. The patient complained of eye pain during extraocular movement (EOM) testing, and pupil testing shows a 2+ afferent pupillary defect. Formal visual field testing shows an inferior altitudinal defect. Your diagnosis? Presumed retrobulbar optic neuritis.
Sixty-six percent of optic neuritis is classified as retrobulbar, which means that in only onethird of optic neuritis cases will you see manifestations at the optic nerve, most commonly edema. After an acute episode of optic neuritis, the vast majority of patients recover at least 20/40 vision or better, with the worse acuity on initial presentation an indicator of poor final acuity. Educate these patients that they are experiencing an ocular manifestation that can be linked to the systemic demyelinating disease multiple sclerosis (MS).
Refer these patients for an MRI, which will identify the presence of white matter demyelinating plaques. MS predominately affects females ages 20 to 40, but don't overlook the possibility of this diagnosis in male patients.
MS is an autoimmune disease affecting the myelin sheath of the central nervous system. Symptoms may include loss of motor coordination and tremor, among many others that can be severely debilitating. Patients may suffer from frequent relapses and remissions, and treatment is aimed at preventing those relapses. Current treatment protocols typically include weekly interferon infusions with such medications as interferon beta-1a or glatiramer acetate, or other immunomodulators including interferon beta-1b, mitoxantrone and natalizumab.
Up to 50% of patients with MS develop an episode of optic neuritis, and from 20% to 30% of the time optic neuritis is the presenting sign of MS. The presence of demyelinating white matter plaques on brain MRI at the time of presentation of optic neuritis is the strongest predictor for developing clinically definite MS. Almost half of the patients with optic neuritis have white matter lesions consistent with MS.
At five years follow-up, the overall risk of developing MS is 30%, with or without MRI lesions. Patients with a normal MRI still develop MS (16%), but at a lower rate compared to those patients with three or more MRI lesions (51%). However, almost half (44%) of patients with any demyelinating lesions on MRI at presentation will not have developed MS 10 years later.7
The 15-year risk of developing MS in the Optic Neuritis Treatment Trial (ONTT) was 25% with no lesions, but 72% with one or more lesions.8 The bottom line is that patients with the presence of brain abnormalities on initial MRI are considerably more likely to develop MS.
Treatment with high-dose IV methylprednisolone is aimed at hastening visual recovery, preventing a recurrence in the other eye and delaying, but not preventing, the onset of MS, though this benefit disappears after three years.
When I encounter a patient who has optic neuritis, I counsel him about the natural history of vision loss, I write an order for an MRI, and I educate him about the need for the MRI and its association with MS. I may also discuss the risks and benefits of IV methylprednisolone in the acute phase.
Prompt referral to the patient's PCP or a neurologist should be given for a definitive diagnosis and, if necessary, to begin treatment.
Systemic inflammatory disease
Recently, I was referred a patient who had a red, painful eye. He had been using loteprednol etabonate and tobramycin ophthalmic suspension (Zylet, Bausch + Lomb) twice a day for a week and taking acetaminophen for the pain. His injection pattern was very deep, with almost a diffuse pinkish hue on the sclera that did not blanch with phenylephrine. With a subtherapeutic dosage of Zylet and the acetaminophen, his symptoms were somewhat dulled, but not eradicated. After ruling out posterior involvement, I diagnosed him with diffuse anterior scleritis and started a course of ibuprofen 400mg to 600mg PO q6h. After one week, with minimal improvement, I asked him to discontinue the non-steroidal antiinflammatory drug (NSAID) and switched him to 60mg of oral prednisone (1 mg/kg of body weight). The improvement in his symptoms was almost instantaneous.
Refer patients who have scleritis to their PCP for a systemic evaluation of underlying causes. Patients who have scleritis and no previous diagnosed systemic disease should be sent for CBC, ESR, uric acid level, RPR, fluorescent treponemal antibody absorbed (FTA-ABS), Rhesus (Rh) factor, ANA and fasting glucose level tests.
A total of 50% of patients who have scleritis also have associated systemic disease. When I questioned the patient about his health, he stated that he has suffered from rheumatoid arthritis (RA) for a few years. In addition to RA, other systemic diseases, including systemic lupus erythematosis, ankylosing spondylitis and polyarteritis nodosa are among those associated with scleritis.
RA is an autoimmune disease in which the body produces IgM (rheumatoid factor) against itself. This leads to high concentrations of tumor necrosis factor alpha in the joints with resulting destruction. Long-term treatment has been aimed at lessening the symptoms, and patients are often prescribed hydroxychloroquine or NSAIDs. Recent research points to more preventing joint destruction by taking tnf-alpha blockers. So, you can expect your patients to be on more aggressive therapies earlier in the course of the disease to prevent long-term joint destruction.
While scleritis remains a serious consequence of RA, it is by no means the most common. In fact, dry eye is present in a large number of patients with RA. Many practitioners have incorporated dry eye follow-ups into the care regimens of these patients. Dry eye follow-ups generate multiple office visits, and patients are very grateful when you are able to help them. Corneal pathology, including peripheral ulceration, may also occur in patients with RA and must be treated promptly to avoid significant ocular morbidity.
The aforementioned conditions are by no means an exhaustive list, but they represent the more common systemic diseases that have ocular manifestations.
Gone are the days of just refracting the patient and wishing him well. Is anything more important to your practice and the future of our profession than finding new ways to deliver more comprehensive care to our patients? Treating your patient as a whole makes both dollars and "sense." Your practice will grow by keeping your existing patients as well as the network of patient referrals you'll generate. With the landscape of healthcare changing, the medical aspects of optometry will also likely continue to grow. Communication amongst professions will be more important than ever — and hopefully, easier with electronic health records — leading to efficient patient care and decreased costs.
So, don't be afraid to delve into a patient's overall health. Often, they'll willingly share their symptoms with you. When faced with the question, "Guess what my eye doctor found?" the answer for you will be a patient for life. OM
1. Flynn HW Jr, Smiddy WE, eds. Diabetes and Ocular Disease: Past, Present, and Future Therapies. Ophthalmology Monograph 14. San Francisco: American Academy of Ophthalmology; 2000:49-53,226.
2. Sonmez B, Bozkurt B, Atmaca A, et. al. Effect of glycemic control on refractive changes in diabetic patients with hyperglycemia. Cornea, 2005 Jul:24(5):531-7.
3. Summary of revisions for the 2010 Clinical Practice Recommendations. Diabetes Care 2010;33:53.
4. Klein. R. Klein BE., Moss SE, Cruickshanks KJ. The Wisconsin epidemologic study of diabetic retinopathy. XIV. Ten-year incidence and progression of diabetic retinopathy. Arch Ophthalmol. 1994 Sep;112(9):1217-28.
5. Hnik P, Boyer DS, et. al. Antisense oligonucleotide therapy in diabetic retinopathy. Diabetes. Sci Technol. 2009 Jul 1:3(4):924-30.
6. Campochiaro PA. Sustained release intravitreal implant II. Paper presented at: Angiogenesis 2010: Clinical Trials; February 20, 2010; Miami, Fla.
7. Optic Neuritis Study Group. Multiple sclerosis risk after optic neuritis: final optic neuritis treatment trial followup. Arch. Neurol. 2008 Jun;65(6):727-32.
8. Optic Neurits Study Group. Multiple sclerosis risk after optic neuritis: final optic neuritis treatment trial followup. Arch Neurol. 2008 Jun;65(6):727-32.
||Dr. Marcolini is vice president of the New Jersey Society of Optometric Physicians (NJSOP). He practices at Omni Eye Services in Iselin, N.J. and Clinton Family Eye Care in Clinton, N.J. Dr. Marcolini has no financial interest in any of the therapies mentioned in this article.
Optometric Management, Issue: July 2010