What's Your Diagnosis?

Woman reports blurry vision at all distances

A 49-year-old African American female presented for a comprehensive exam secondary to blurry vision at distance with her habitual spectacle prescription from her last comprehensive eye exam, 2 years prior. After further questioning, the change was described as insidious, occurring at all distances, and more pronounced in the right eye.

The patient’s ocular history was remarkable for retinitis pigmentosa, which was diagnosed 15 years prior. She reported reduction of her peripheral vision, which impaired her driving to the extent that she had discontinued it. The family history was negative for pertinent ocular conditions. She specifically denied any previous ocular trauma and long-term medication use. Her medical history was significant only for fibromyalgia. No ocular or systemic medications were reported.

Sarah Marietta

Entering acuities were 20/30-2 OD and 20/20 OS, with +1.00 D -1.25 D x 105 OD and +1.25 D -1.00 D x 080 OS. Manifest refraction was +1.00 D -2.00 D x 105 OD and +1.25 D -1.50 D x 080 OS without improvement in best-corrected visual acuity. Extraocular movements were full in the right and left eyes. Pupils were equal in size and reactive to light with no relative afferent pupillary defect in either eye. Confrontation fields were severely constricted in each eye. The anterior segments were unremarkable except for trace nuclear sclerosis of each eye. Intraocular pressures were 14 mm Hg OD and 14 mm Hg OS by Goldmann at 8:30 a.m.

Fundus examination revealed healthy optic nerves with normal vasculature of both eyes. However, the macula of the right eye appeared to be thickened, while the left macula was unremarkable. An atypical presentation of bone spicules was noted in both eyes with pigmentation found circumferential to the disc and macula without typical midperipheral involvement.

In the absence of ocular trauma and any long-term medication use that may alter retinal pigmentation, the differential diagnoses are limited. The previous diagnosis of retinitis pigmentosa substantiates the clinical findings.

Retinitis pigmentosa (RP) is an inherited retinal dystrophy belonging to the group of pigmentary retinopathies. It is a degenerative retinal disease caused by the loss of photoreceptors and characterized by the clinical appearance of pigment deposits known as “bone spicules” noted on peripheral fundus examination. Classic RP is often described as a rod-cone dystrophy; accordingly, in RP, nyctalopia and peripheral vision loss often precede loss of central visual acuity.

Fundus photos show bone spicule pigmentation circumferential to the optic nerve and macula in both eyes. The vasculature is normal.

Images: Marietta S

Central visual acuity can be reduced at any stage of disease, with the final expected acuity predicted by the individual mode of inheritance. The autosomal dominant forms tend to be less severe than either the autosomal recessive or X-linked forms. Common causes of reduced acuity in these patients are posterior subscapular cataracts and maculopathy, with the former modifiable through surgical intervention. Maculopathy may be further subdivided into cystic edema, epiretinal membrane (ERM) or degeneration of the retinal pigment epithelium (RPE).

Fundus exam, OCT

Fundus autofluorescence of the right eye shows the petalloid presentation of the cystic spaces.

Subtle macular changes may be difficult to discern with fundus examination. OCT is a powerful supplementary tool useful in determining the cause in patients with decreased acuity where fundus examination is equivocal. In our patient, spectral domain OCT (SD-OCT) revealed cystic spaces without preretinal fibrosis, disruption of the RPE or loss of the overlying photoreceptor integrity line. Central foveal thickness was measured to be 480 microns. Fundus autofluorescence (FAF) additionally demonstrated cystoid macular edema’s (CME’s) characteristic petalloid appearance, subclinical to funduscopy.

CME is a potentially chronic complication of RP and may cause permanent reduced central acuity affecting up to 40% of patients (Ikeda et al., 2013). This condition is secondary to the breakdown of the blood-retinal barrier. Although the exact pathophysiology remains poorly understood, the condition is presumed to be multifactorial. Underscoring this presumption is the fact that traction from an ERM can cause cystic spaces. However, in the absence of an ERM there is speculation that faulty RPE pumps are to blame.

Treatment: Oral vs. topical

Oral carbonic anhydrase inhibitors (CAIs) have been the mainstay of CME treatment for years. It is believed that CAIs decrease CME by increasing the available carbonic anhydrase, which is hypothesized to increase efficacy of the RPE pumps, thus improving fluid transport from the retina to the choroid.

Acetazolamide, 500 mg once a day, is the typical treatment of choice. However, oral CAIs are often discontinued prematurely because of the medication’s many side effects including: paresthesia, fatigue, gastrointestinal intolerance, loss of appetite, kidney stones and hypokalemia. Due to the potassium wasting effects, potassium levels must be monitored periodically, adding an additional level of complexity to the management of patients on oral CAIs. Common ocular side effects of topical CAIs are burning, itching, redness and blurred vision. In addition, the medication, like other ocular hypotensive agents, may cause a substantial decrease in IOP.

Given their superior safety profile, topical alternatives have become a more recent focus of research. Multiple studies have now demonstrated that topical dorzolamide dosed three times per day reduces central foveal thickness in 80% or more of patients (Bartlett et al.; Fishman et al.; Liew et al.; Ikeda et al., 2012; Apushkin et al.; Grover et al.). The effects of topical dorzolamide may not be immediate; a patient’s response to treatment may be assessed within 6 months of initiating it (Ikeda et al., 2013).

Managing CME in these patients can be frustrating to both clinician and patient alike because, contrary to common belief, visual acuity often does not correlate to the reduction in the cystic lesions. Furthermore, rebound macular edema has been documented with prolonged CAI treatment in as many as 20% of cases (Salvatore et al., Fishman et al., Genead et al.). However, a case study of three patients demonstrated that discontinuation of CAI therapy for a period of 2 months to 5 months can restore the therapy’s effectiveness (Thobani et al.).

Our patient’s management

Initial presentation of cystoid macular edema in the right eye.

The patient was started on topical dorzolamide three times a day in the right eye only and scheduled to return in 8 weeks. No new spectacle correction was recommended at this exam.

At the 8-week follow-up exam, the patient denied any changes in her vision and reported good compliance with medication. While the patient denied improvement in her vision, both eyes were correctable to 20/20. IOPs were 13 mm Hg OD and 13 mm Hg OS by Goldmann at 8:55 a.m.

Comparative SD-OCT was used to determine change in the macular thickness. At the 8-week follow-up exam, macular thickness was 250 microns, which was substantially reduced from the 480 microns at the baseline exam, with restoration of the normal foveal contour and two isolated large cystic spaces remaining. Thus, the patient was to continue dorzolamide three times daily in the right eye only and return to clinic in another 8 weeks.

SD-OCT of the right eye at the 8-week follow-up exam. The normal foveal contour was restored, and two isolated large cystic spaces remained.

The 16-week follow-up exam revealed stable BCVA of 20/20 in both eyes and further improvement in central macular thickness with a few fine cystic spaces now remaining. IOPs remained 13 mm Hg OD and 13 mm Hg OS with Goldmann at 8:27 a.m. Therefore, the patient was advised to continue the current medication and return for follow-up 3 to 4 months later. Additional follow-up information has not been determined at this time.

Dorzolamide first-line therapy

Given its proven safety and effectiveness in the literature, topical dorzolamide should be considered as a first-line therapy for CME in patients with RP. This choice potentially allows these patients to remain in the optometric physician’s office, improving efficiency and continuity of care and eliminating specialist referrals.

SD-OCT of the right eye at the 16-week follow-up exam. The macular thickness is reduced by about 200 microns from the initial exam, and a few fine cystic spaces remained.

It is crucial that these patients be monitored routinely for changes, as not all patients respond favorably to topical treatment, and rebound CME is a common complication. Alternative treatments, such as oral acetazolamide, should be considered in such cases. The Aflibercept for macular oedema with underlying retinitis pigmentosa (AMOUR) study is currently recruiting patients.

Disclosure: The author reports no relevant financial disclosures.

A 49-year-old African American female presented for a comprehensive exam secondary to blurry vision at distance with her habitual spectacle prescription from her last comprehensive eye exam, 2 years prior. After further questioning, the change was described as insidious, occurring at all distances, and more pronounced in the right eye.

The patient’s ocular history was remarkable for retinitis pigmentosa, which was diagnosed 15 years prior. She reported reduction of her peripheral vision, which impaired her driving to the extent that she had discontinued it. The family history was negative for pertinent ocular conditions. She specifically denied any previous ocular trauma and long-term medication use. Her medical history was significant only for fibromyalgia. No ocular or systemic medications were reported.

Sarah Marietta

Entering acuities were 20/30-2 OD and 20/20 OS, with +1.00 D -1.25 D x 105 OD and +1.25 D -1.00 D x 080 OS. Manifest refraction was +1.00 D -2.00 D x 105 OD and +1.25 D -1.50 D x 080 OS without improvement in best-corrected visual acuity. Extraocular movements were full in the right and left eyes. Pupils were equal in size and reactive to light with no relative afferent pupillary defect in either eye. Confrontation fields were severely constricted in each eye. The anterior segments were unremarkable except for trace nuclear sclerosis of each eye. Intraocular pressures were 14 mm Hg OD and 14 mm Hg OS by Goldmann at 8:30 a.m.

Fundus examination revealed healthy optic nerves with normal vasculature of both eyes. However, the macula of the right eye appeared to be thickened, while the left macula was unremarkable. An atypical presentation of bone spicules was noted in both eyes with pigmentation found circumferential to the disc and macula without typical midperipheral involvement.

In the absence of ocular trauma and any long-term medication use that may alter retinal pigmentation, the differential diagnoses are limited. The previous diagnosis of retinitis pigmentosa substantiates the clinical findings.

Retinitis pigmentosa (RP) is an inherited retinal dystrophy belonging to the group of pigmentary retinopathies. It is a degenerative retinal disease caused by the loss of photoreceptors and characterized by the clinical appearance of pigment deposits known as “bone spicules” noted on peripheral fundus examination. Classic RP is often described as a rod-cone dystrophy; accordingly, in RP, nyctalopia and peripheral vision loss often precede loss of central visual acuity.

Fundus photos show bone spicule pigmentation circumferential to the optic nerve and macula in both eyes. The vasculature is normal.

Images: Marietta S

Central visual acuity can be reduced at any stage of disease, with the final expected acuity predicted by the individual mode of inheritance. The autosomal dominant forms tend to be less severe than either the autosomal recessive or X-linked forms. Common causes of reduced acuity in these patients are posterior subscapular cataracts and maculopathy, with the former modifiable through surgical intervention. Maculopathy may be further subdivided into cystic edema, epiretinal membrane (ERM) or degeneration of the retinal pigment epithelium (RPE).

Fundus exam, OCT

Fundus autofluorescence of the right eye shows the petalloid presentation of the cystic spaces.

Subtle macular changes may be difficult to discern with fundus examination. OCT is a powerful supplementary tool useful in determining the cause in patients with decreased acuity where fundus examination is equivocal. In our patient, spectral domain OCT (SD-OCT) revealed cystic spaces without preretinal fibrosis, disruption of the RPE or loss of the overlying photoreceptor integrity line. Central foveal thickness was measured to be 480 microns. Fundus autofluorescence (FAF) additionally demonstrated cystoid macular edema’s (CME’s) characteristic petalloid appearance, subclinical to funduscopy.

CME is a potentially chronic complication of RP and may cause permanent reduced central acuity affecting up to 40% of patients (Ikeda et al., 2013). This condition is secondary to the breakdown of the blood-retinal barrier. Although the exact pathophysiology remains poorly understood, the condition is presumed to be multifactorial. Underscoring this presumption is the fact that traction from an ERM can cause cystic spaces. However, in the absence of an ERM there is speculation that faulty RPE pumps are to blame.

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Treatment: Oral vs. topical

Oral carbonic anhydrase inhibitors (CAIs) have been the mainstay of CME treatment for years. It is believed that CAIs decrease CME by increasing the available carbonic anhydrase, which is hypothesized to increase efficacy of the RPE pumps, thus improving fluid transport from the retina to the choroid.

Acetazolamide, 500 mg once a day, is the typical treatment of choice. However, oral CAIs are often discontinued prematurely because of the medication’s many side effects including: paresthesia, fatigue, gastrointestinal intolerance, loss of appetite, kidney stones and hypokalemia. Due to the potassium wasting effects, potassium levels must be monitored periodically, adding an additional level of complexity to the management of patients on oral CAIs. Common ocular side effects of topical CAIs are burning, itching, redness and blurred vision. In addition, the medication, like other ocular hypotensive agents, may cause a substantial decrease in IOP.

Given their superior safety profile, topical alternatives have become a more recent focus of research. Multiple studies have now demonstrated that topical dorzolamide dosed three times per day reduces central foveal thickness in 80% or more of patients (Bartlett et al.; Fishman et al.; Liew et al.; Ikeda et al., 2012; Apushkin et al.; Grover et al.). The effects of topical dorzolamide may not be immediate; a patient’s response to treatment may be assessed within 6 months of initiating it (Ikeda et al., 2013).

Managing CME in these patients can be frustrating to both clinician and patient alike because, contrary to common belief, visual acuity often does not correlate to the reduction in the cystic lesions. Furthermore, rebound macular edema has been documented with prolonged CAI treatment in as many as 20% of cases (Salvatore et al., Fishman et al., Genead et al.). However, a case study of three patients demonstrated that discontinuation of CAI therapy for a period of 2 months to 5 months can restore the therapy’s effectiveness (Thobani et al.).

Our patient’s management

Initial presentation of cystoid macular edema in the right eye.

The patient was started on topical dorzolamide three times a day in the right eye only and scheduled to return in 8 weeks. No new spectacle correction was recommended at this exam.

At the 8-week follow-up exam, the patient denied any changes in her vision and reported good compliance with medication. While the patient denied improvement in her vision, both eyes were correctable to 20/20. IOPs were 13 mm Hg OD and 13 mm Hg OS by Goldmann at 8:55 a.m.

Comparative SD-OCT was used to determine change in the macular thickness. At the 8-week follow-up exam, macular thickness was 250 microns, which was substantially reduced from the 480 microns at the baseline exam, with restoration of the normal foveal contour and two isolated large cystic spaces remaining. Thus, the patient was to continue dorzolamide three times daily in the right eye only and return to clinic in another 8 weeks.

SD-OCT of the right eye at the 8-week follow-up exam. The normal foveal contour was restored, and two isolated large cystic spaces remained.

The 16-week follow-up exam revealed stable BCVA of 20/20 in both eyes and further improvement in central macular thickness with a few fine cystic spaces now remaining. IOPs remained 13 mm Hg OD and 13 mm Hg OS with Goldmann at 8:27 a.m. Therefore, the patient was advised to continue the current medication and return for follow-up 3 to 4 months later. Additional follow-up information has not been determined at this time.

Dorzolamide first-line therapy

Given its proven safety and effectiveness in the literature, topical dorzolamide should be considered as a first-line therapy for CME in patients with RP. This choice potentially allows these patients to remain in the optometric physician’s office, improving efficiency and continuity of care and eliminating specialist referrals.

SD-OCT of the right eye at the 16-week follow-up exam. The macular thickness is reduced by about 200 microns from the initial exam, and a few fine cystic spaces remained.

It is crucial that these patients be monitored routinely for changes, as not all patients respond favorably to topical treatment, and rebound CME is a common complication. Alternative treatments, such as oral acetazolamide, should be considered in such cases. The Aflibercept for macular oedema with underlying retinitis pigmentosa (AMOUR) study is currently recruiting patients.

Disclosure: The author reports no relevant financial disclosures.