Asymptomatic contact lens patient has pigmented fundus lesions

David W. Nelson

A 27-year-old man presented for a routine examination to refill a prescription for contact lenses. He was asymptomatic for vision problems. His personal health history was negative and he was taking no medications.

A full examination was performed. The patient’s best-corrected visual acuity was 20/20 in each eye with OD -1.00 -0.50 x 015 and OS -0.75 -1.25 x 150. The anterior segment, color vision and stereo were all normal. Noncontact tonometry pressures were 14 mm Hg OD and 16 mm Hg OS. Blood pressure was 114/82 mm Hg. His past medical history was significant for nasal allergies relieved by a nasal steroid spray. His past family medical history was significant for glaucoma (uncle) and cataracts (grandmother).

The Optomap images revealed that the lesions were visible in all quadrants of both eyes. Images: Nelson DW

The lesions were slightly visible using red-free filtering light.

The lesions were quite visible using green-free light.

The only finding of significance was the appearance of multiple, flat pigmented lesions in the retina of both eyes. Upon further observation with red- and green-free light, it was found that the lesions were quite visible using green-free light. The lesions were slightly visible using red-free filtering light, not completely disappearing.

The Optomap images revealed that the lesions were visible in all quadrants of both eyes.

What is your diagnosis?

A young man with bilateral multiple, flat pigmented lesions in the retina at the level of the retinal pigment epithelium (RPE) should be observed with red- and green-filtered light to determine the lesions’ depth. The differential diagnoses would include choroidal nevi, any of the various presentations of congenital hypertrophy of the RPE (CHRPE), choroidal melanoma and the remodeling processes of other various inflammatory lesions.

In this case, the red-free and green-free observations show multiple flat pigmented lesions that are slightly visible in the red-free light and quite visible in the green-free Optomap images.

Choroidal nevi would be absent in the red-free images, thus, this condition can be ruled out. Melanoma would also be present in both red-free and green-free images and would likely be observed to be elevated with stereoscopic examination and if a B-scan were performed. However, the clusters of pigmented lesions and the absence of inflammatory signs point to another diagnosis, CHRPE.

Usually, CHRPE is unilateral and most likely found in the peripheral retina. However, when the RPE is hypertrophied in both eyes, Gardner’s syndrome is highly suspected.

Due to the systemic and genetic nature of this syndrome, patients must be informed and counseled for further work-ups, particularly a gastrointestinal evaluation for polyps or possible colorectal cancer. According to Regillo and colleagues, polyps have a 100% risk of undergoing malignant transformation; consequently, early identification of Gardner’s syndrome is critical. All first-degree relatives of patients with Gardner’s syndrome or familial adenomatous polyposis (FAP) should be screened.

Most likely diagnosis

CHRPE lesions are flat, pigmented lesions that can appear in single or multifocal lesions, often in a single quadrant of the retina. The single CHRPE lesion often has scalloped edges, lacunae (depigmented areas within lesion) and a halo of hypopigmentation.

Grouped pigmentations are often called “bear-tracks” due to their characteristic footprint or animal track appearance. These lesions are usually larger in the periphery and become smaller in size closer to the optic disc. CHRPE used to be considered stable, unchanging lesions; however, recent research by Shields and colleagues on more than 300 patients has shown that the lesions enlarged 83% of the time, with the average increase of 10 µm per month over a 3-year period.

The lesions are differentiated from choroidal nevi by the use of filtered observation with red-free and green-free light. While the choroidal nevus is below the RPE, the use of red-free light will hide the nevus, but not the CHRPE. Additionally, choroidal nevi are rarely jet black, have ill-defined borders and often are slightly elevated, according to Shields and colleagues. The use of green-free light will allow observation of both nevi and CHRPE.

The Optomap uses two wavelengths of laser light, a green laser at 532 nm and a red laser at 633 nm, which is particularly helpful in identifying the difference by clicking the red channel monitor.

Ocular coherence tomography (OCT) can further differentiate isolated and grouped, multifocal CHRPE lesions. The OCT section of a single CHRPE lesion may show a much greater thickening of the RPE and an overlying retinal thinning than the multiple lesions.

In the case of isolated CHRPE, the overlying retinal thinning is a result of photoreceptor loss. This would manifest a corresponding visual field defect.

Early diagnosis critical

Gardner’s syndrome is a variant of FAP with extra-colonic manifestations, multiple osteomas and skin and soft tissue tumors first described by Eldon Gardner in 1950. It is genetically linked to band 5q21, the adenomatous polyposis coli locus FAP, which, in 80% of cases, is transmitted in an autosomal dominant fashion.

Cutaneous findings of Gardner’s syndrome include epidermoid cysts, desmoid tumors and other benign tumors, according to Ascari-Raccagni and colleagues. Again, polyps have a 100% risk of undergoing malignant transformation, according to Hood and Krush; consequently, early identification of Gardner’s syndrome is critical.

Pathophysiology

Shields reported that FAP and Gardner’s syndrome are believed to be variants of the same condition. The wider spectrum of abnormalities found in Gardner’s syndrome may represent variable penetrance of a common genetic mutation. Normally, the APC gene helps control cell growth; however, when mutation occurs, cell growth accelerates out of control.

According to Schwartz, one person per million population is diagnosed with Gardner’s syndrome. The incidence of FAP is one case per 8,000 people.

The most common cutaneous finding in patients with Gardner’s syndrome is epidermoid cysts (50% to 65%). Unless surgical transection is performed, GI polyps may progress to malignancy in nearly 100% of Gardner’s syndrome patients (rates vary from 58% to 100% in studies).

Although colonic polyps begin to form in puberty, the average age at Gardner’s syndrome diagnosis is 22 years. Osteoma formation precedes polyposis. Usually, progression to malignancy is observed in patients 30 to 50 years old. The average age by which malignancy is diagnosed is 39.2 years.

Many skin findings of Gardner’s syndrome are evident on full body examination; however, the patient’s history at the age of onset and whether lesions are present in family members is important. Cysts in patients with Gardner’s syndrome are usually asymptomatic, but they may be pruritic or inflamed. More than half the patients with this syndrome have dental anomalies, according to Madani and Madani. Previously undiagnosed Gardner’s syndrome may be detected when the patient is evaluated for multiple impacted and unerupted teeth.

As FAP progresses, a patient may experience bleeding, diarrhea, fatigue and malnutrition as a result of the colonic polyps. A patient is diagnosed by the direct observation of these colonic polyps during a colonoscopy.

Other studies may be performed, including testing for APC gene mutation, a CT scan of the abdomen or by viewing the extra-colonic manifestations of Gardner’s syndrome through various techniques. These extra-colonic manifestations include, but are not limited to, intestinal polyposis, dental abnormalities and osteomas.

Intestinal polyps often form in the duodenum and are evaluated by esophagogastroduodenoscopy. Dental abnormalities involve supernumerary teeth or unerupted teeth, which often result in jaw pain. Osteomas are benign bone tumors observed through radiographs of the chest or skull. In addition, Schwartz reported that congenital hypertrophy of the retinal pigment epithelium (CHRPE) is seen in 58% to 88% of cases. Remember that grouped retinal pigment, CHRPE, is an extra-colonic manifestation, as well.

Medical care

After a patient is diagnosed, FAP may be managed by surgical intervention and through the use of medications. As 100% of cases will develop colonic adenoma-related cancer, surgery should be performed shortly after diagnosis. According to Schwartz, the 5-year survival rate of patients older than 45 who do not undergo surgery is 0%; however, the 5-year survival rate of patients who do have surgery is almost 100%.

The risk of recurrent carcinoma is 12% to 32% in 20 years and 45% in 30 years. Drugs such as sulindac and doxorubicin have been shown to reduce polyps following total colectomy.

Patients who are diagnosed with FAP should receive yearly follow-up to monitor any extra-colonic manifestations. Patients who have a CHRPE lesion should also be followed up periodically as there is a small chance that a CHRPE lesion may progress into a neoplasm.

Follow-up for this patient

This patient was referred to the University of Wisconsin-Madison Retina Department for confirmation of Gardner’s syndrome. A retinal specialist there concurred with the diagnosis and sent the patient for a gastrointestinal workup. The colonoscopy was normal, with no polyps noted.

There was no knowledge of a family history of this typically hereditary systemic disorder. The patient was counseled that his siblings and immediate family members all must be notified regarding their own medical interests, particularly early colonoscopies. This patient must undergo a colonoscopy every 3 to 5 years, indefinitely.

References:

• Ahn ES, Singh AD. Isolated anomaly of the retinal pigment epithelium. Advanced Ocular Care. http://bmctoday.net/advancedocularcare/2010/03/article.asp?f=isolated-anomaly-of-the-retinal-pigment-epithelium. Updated March 2010. Accessed July 27, 2010.
• Ascari-Raccagni A, Baldari U, Righini MG. Cutaneous symptoms of Gardner’s syndrome. J Eur Acad Dermatol Venereol. 1999;12(1):80-81.
• Coleman P, Bernard NAS. Congenital hypertrophy of the retinal pigment epithelium: Prevalence and ocular features in the iptometric population. Ophthal Physiol Opt. 2007;27:547-555.
• Hood AB, Krush AJ. Clinical and dermatologic aspects of the hereditary intestinal polyposes. Dis Colon Rectum. 1983;26(8):546-548.
• Madani M, Madani F. Gardner’s syndrome presenting with dental complaints. Arch Iran Med. 2007;10(4):535-539.
• Regillo CD, Eagle RC, Shields JA, Chields CL, Arbizo W. Histopathologic findings in the congenital grouped pigmentation of the retina. Ophthalmology. 1993;100:400-405.
• Schwartz RA. Gardner syndrome. http://emedicine.medscape.com/article/1093486-overview. Updated June 23, 2010. Accessed July 27, 2010.
• Shields CL, Mashayekhi A, Ho T, Cater J, Shields JA. Solitary congenital hypertrophy of the retina pigment epithelium: Clinical features and frequency of enlargement in 330 patients. Ophthalmology. 2003;100:1968-1976.
• Shields JA. Diagnosis and Management of Intraocular Tumors. St. Louis, MO: CV Mosby Company; 1983.

• David W. Nelson, OD, MBA, a former president of the American Optometric Association, is in private practice in Madison, Wis. He provides consulting and educational lectures across the United States on newly advancing areas of retinal imaging. Dr. Nelson can be reached at 7428 Mineral Point Road, Madison, WI 53717; (608) 833-4242; fax: (608) 833-4248; amoptbddwn@aol.com. Dr. Nelson has no direct financial interest in the products mentioned in this article but is a paid consultant to Optos and chair of the company’s Primary Eye Care Council.
• Matthew T. Nelson is a senior at Vanderbilt University majoring in neuroscience. He plans to apply to medical school this fall. He can be reached at matthew.t.nelson@vanderbilt.edu. Mr. Nelson has no direct financial interest in the products mentioned in this article, nor is he a paid consultant for any companies mentioned.