What's Your Diagnosis?

Woman suddenly loses central vision

Fundus photos of the right (top) and left eyes.
Source: Leonid Skorin Jr., OD, DO, MS, FAAO, FAOCO

A 39-year-old Caucasian woman presented complaining of a dark spot in the central vision of her right eye that began 3 days prior. The dark spot was accompanied by a heavy, pressure-like sensation in the right eye. She had never experienced these symptoms before and had no previous history of trauma. She denied having any flashes or floaters.

The patient’s medical history was significant for scleroderma morphea and migraines. There was a family history of systemic lupus erythematosus and diabetes mellitus. Her medications included alprazolam, topiramate, quetiapine fumarate and a transdermal etonogestrel implant. She denied any drug allergies.

Macular OCT of the right and left eyes.

When the patient was seen 10 years prior for her first eye exam, multiple yellow-white lesions were noted in the retina of the right eye, and a single yellow-white lesion was noted in the left eye. At that visit her best corrected visual acuity was 20/20 in each eye. All other findings were unremarkable including vitreous, discs and macula. Refraction revealed emmetropia with a visual acuity of 20/20 in each eye. Several lab tests were ordered, including erythrocyte sedimentation rate, complete blood count, antinuclear antibody, angiotensin converting enzyme, rapid plasma reagin and fluorescent treponemal antibody absorption. All were negative or within normal range. At her initial visit, the retinal lesions were thought to be viral in nature. The patient was monitored for 3 months before the lesions were determined to be stable and noncompromising to her vision.

During our examination, 10 years later, the patient had a visual acuity of 20/175 OD with eccentric viewing and no improvement on pinhole and 20/20 OS. Pupils were equal, round and reactive to light with no afferent pupillary defect in either eye. Extraocular muscle function was full, with no pain or diplopia. Confrontation fields were full to finger count in both eyes. IOP was 22 mm Hg in each eye. Anterior segment examination was unremarkable.

Early stage fluorescein angiography of the right and left eyes. Right eye: 37 seconds, left eye: 28 seconds.

Posterior segment evaluation revealed optic nerves with distinct margins, perfused rim tissue and cup-to-disc ratios of 0.2 in both eyes. The vessels in each eye were of normal caliber with no sheathing. The periphery was flat with no holes, tears or detachments in either eye. The macula of both eyes had multiple small, yellow-white perimacular lesions with indistinct borders that appeared to involve the deeper retina. There were more lesions in the right eye, with one large foveal lesion and a patch of hypopigmentation along the superior arcades.

The patient was referred to a retina specialist who saw her 9 days later. At that time, the patient reported some improvement in the vision of the right eye. Her central blind spot was also diminished in size. Her best corrected visual acuity was improved to 20/60 OD with no improvement upon pinhole testing and 20/20 OS. Pupils were equal, round and reactive to light with no relative afferent pupillary defect, and IOPs were 19 mm Hg OD and 21 mm Hg OS.

Late stage fluorescein angiography of the right and left eyes. Right eye: 13:57 minutes, left eye: 13:49 minutes.

A macular OCT and fluorescein angiography were performed on the patient.

What’s your diagnosis?
See answer on page 20.

The patient history and clinical findings are consistent with punctate inner choroidopathy of both eyes and choroidal neovascular membrane in the right eye.

Punctate inner choroidopathy (PIC) is a type of posterior uveitis. It is one of a group of inflammatory disorders known as the white dot syndromes that are differentiated by presentation, laterality, history and fluorescein angiogram findings.

PIC typically presents in 20- to 40-year-old myopic women. Although our patient was emmetropic, she was found to have this condition in her late 20s and experienced complications in her late 30s. In a 2007 survey, 26% of PIC patients surveyed reported a family history of autoimmune diseases including systemic lupus erythematosus, which our patient had in her family history (Radgonde et al.). There is a possible genetic connection of autoimmune disease, which includes the patient’s scleroderma morphea, and inflammatory conditions such as the white dot syndromes.

Marisa Asheim

Evaluation

A diagnosis of PIC is based on clinical findings with a bilateral presentation of multiple small, discrete, yellow or white spots in the fundus with little or no intraocular inflammation. Fluorescein angiography will show early hyperfluorescence and late staining of the lesions. As the lesions resolve over the course of several weeks, they may leave atrophic chorioretinal scars.

Leonid Skorin Jr.

Choroidal neovascular membranes (CNVMs) and resultant serous retinal detachments or edema can occur in 40% of patients, usually over subretinal scars (Radgonde et al.). Patients have an increased risk of developing CNVM with the presence of CNVM in the fellow eye. Our patient’s presentation was different in that the subfoveal CNVM occurred with an active lesion rather than an atrophic scar.

Differential diagnosis

Several systemic conditions should be considered as differential diagnoses with PIC and were ruled out in her initial exam. These include presumed ocular histoplasmosis, sarcoidosis, myopic degeneration maculopathy, infectious etiologies (viral, bacterial, fungal, protozoan and helminthic), other white dot syndromes and neoplasm.

Treatment

Typically, no treatment of PIC is needed because the lesions tend to be self-limiting. In the case of subfoveal CNVM, photodynamic therapy (PDT) can be used, or intravitreal anti-VEGF agents are indicated as experimental treatment. For juxtafoveal or extrafoveal CNVM, focal laser photocoagulation should be considered. There is evidence suggesting intravitreal anti-VEGF injections of 1.25 mg bevacizumab can result in stabilization or improvement of vision and reduction of macular edema for both subfoveal and juxtafoveal CNVM (Zhang et al.). Treatment with steroids is controversial, but oral or intravitreal corticosteroid may be added if no improvement is found with anti-VEGF treatment alone. Intravitreal bevacizumab and dexamethasone treatments may encourage longer periods of stability and prevent severe fibrosis.

Prognosis

Macular OCT of the right eye 4 weeks after initial anti-VEGF injection

The prognosis of PIC depends on whether CNVM develops. If no CNVM occurs, visual acuity typically is 20/40 or better. If CNVM threatens the fovea, significant vision loss can result.

Case outcome

Our patient received a 1.25-mg bevacizumab intravitreal injection in her right eye at her visit to the retina specialist. At her 4-week follow-up visit with the retina specialist, her visual acuity in the right eye had improved from 20/60 to 20/30-2. OCT showed reduction in the inflammatory component of the lesions. There was persistent subfoveal fluid of the right eye on OCT, so another 1.25-mg bevacizumab intravitreal injection was performed.

Two weeks later, her visual acuity had improved by one line, to 20/25-2 OD and 20/20 OS. Oral corticosteroid treatment was discussed as an option if intravitreal anti-VEGF treatment did not provide any further improvement in visual acuity going forward. In our patient, oral corticosteroids would be preferred over intravitreal dexamethasone because she is phakic and has a clear natural lens. Intravitreal corticosteroids have a propensity to accelerate cataract formation.

Other white dot syndromes

Other white dot syndromes may look similar to PIC, and none more so than multifocal choroiditis (MFC) with panuveitis. It is thought that these are variations of the same condition, with MFC having a more inflammatory presentation.

MFC typically presents in 20- to 60-year-old healthy Caucasian women. The presentation is similar to PIC, with multiple yellow or gray lesions in the fundus that show early hyperfluorescence and late staining of the lesions. MFC will show more anterior chamber inflammation and vitritis than PIC and may respond better to corticosteroid treatment.

Birdshot retinochoroidopathy occurs in an older population than most of the white dot syndromes, with 40- to 60-year-old Caucasian women being the most commonly affected. This condition has a strong association with HLA-A29. The fundus will have multiple small, scattered, ill-defined, creamy yellow spots on the retina. Birdshot retinochoroidopathy almost always presents with moderate vitritis and no anterior chamber inflammation. The prognosis is variable because the condition is progressive, and in the later stages arteriolar narrowing, macular edema and CNVM can occur.

Serpiginous choroiditis affects men and women equally and occurs in 30- to 60-year-olds. This bilateral condition will show geographic gray-white lesions that begin either near the macula or the peripapillary region and resemble jigsaw puzzle pieces in shape. These lesions will heal into atrophic scars and result in loss of the retinal pigment epithelium, choriocapillaris and choroid. Active lesions are associated with subretinal fluid and are usually adjacent to older, atrophic scars. This disease is progressive and can lead to eventual CNVM and subsequent retinal detachment.

Multiple evanescent white dot syndrome (MEWDS) typically occurs in 20- to 30-year-old females after a viral prodrome. It presents as a granular appearance to the fovea and multiple small, discrete, white lesions of the retinal pigment epithelium. MEWDS may also present with an afferent pupillary defect, vitritis, optic disc edema, paracentral scotoma, central scotoma or an enlarged blind spot. Fundus autofluorescence will show early hyperfluorescence in a wreath-like pattern followed by late staining. Most spontaneously resolve and experience vision improvement in 7 to 10 weeks.

Acute posterior multifocal placoid pigment epitheliopathy occurs equally in males and females between the ages of 20 and 50 years. There is a strong association with HLA-B7 and HLA-DR2. This condition presents bilaterally with large, yellow-white geographic lesions that scar and atrophy over 1 to 2 weeks. Fundus autofluorescence will show early hypofluorescence and late staining of placoid lesions. No treatment is necessary, but corticosteroids may be used if sight-threatening lesions occur.

Disclosures: Asheim and Skorin report no relevant financial disclosures.

Fundus photos of the right (top) and left eyes.
Source: Leonid Skorin Jr., OD, DO, MS, FAAO, FAOCO

A 39-year-old Caucasian woman presented complaining of a dark spot in the central vision of her right eye that began 3 days prior. The dark spot was accompanied by a heavy, pressure-like sensation in the right eye. She had never experienced these symptoms before and had no previous history of trauma. She denied having any flashes or floaters.

The patient’s medical history was significant for scleroderma morphea and migraines. There was a family history of systemic lupus erythematosus and diabetes mellitus. Her medications included alprazolam, topiramate, quetiapine fumarate and a transdermal etonogestrel implant. She denied any drug allergies.

Macular OCT of the right and left eyes.

When the patient was seen 10 years prior for her first eye exam, multiple yellow-white lesions were noted in the retina of the right eye, and a single yellow-white lesion was noted in the left eye. At that visit her best corrected visual acuity was 20/20 in each eye. All other findings were unremarkable including vitreous, discs and macula. Refraction revealed emmetropia with a visual acuity of 20/20 in each eye. Several lab tests were ordered, including erythrocyte sedimentation rate, complete blood count, antinuclear antibody, angiotensin converting enzyme, rapid plasma reagin and fluorescent treponemal antibody absorption. All were negative or within normal range. At her initial visit, the retinal lesions were thought to be viral in nature. The patient was monitored for 3 months before the lesions were determined to be stable and noncompromising to her vision.

During our examination, 10 years later, the patient had a visual acuity of 20/175 OD with eccentric viewing and no improvement on pinhole and 20/20 OS. Pupils were equal, round and reactive to light with no afferent pupillary defect in either eye. Extraocular muscle function was full, with no pain or diplopia. Confrontation fields were full to finger count in both eyes. IOP was 22 mm Hg in each eye. Anterior segment examination was unremarkable.

Early stage fluorescein angiography of the right and left eyes. Right eye: 37 seconds, left eye: 28 seconds.

Posterior segment evaluation revealed optic nerves with distinct margins, perfused rim tissue and cup-to-disc ratios of 0.2 in both eyes. The vessels in each eye were of normal caliber with no sheathing. The periphery was flat with no holes, tears or detachments in either eye. The macula of both eyes had multiple small, yellow-white perimacular lesions with indistinct borders that appeared to involve the deeper retina. There were more lesions in the right eye, with one large foveal lesion and a patch of hypopigmentation along the superior arcades.

The patient was referred to a retina specialist who saw her 9 days later. At that time, the patient reported some improvement in the vision of the right eye. Her central blind spot was also diminished in size. Her best corrected visual acuity was improved to 20/60 OD with no improvement upon pinhole testing and 20/20 OS. Pupils were equal, round and reactive to light with no relative afferent pupillary defect, and IOPs were 19 mm Hg OD and 21 mm Hg OS.

Late stage fluorescein angiography of the right and left eyes. Right eye: 13:57 minutes, left eye: 13:49 minutes.

A macular OCT and fluorescein angiography were performed on the patient.

What’s your diagnosis?
See answer on page 20.

PAGE BREAK

The patient history and clinical findings are consistent with punctate inner choroidopathy of both eyes and choroidal neovascular membrane in the right eye.

Punctate inner choroidopathy (PIC) is a type of posterior uveitis. It is one of a group of inflammatory disorders known as the white dot syndromes that are differentiated by presentation, laterality, history and fluorescein angiogram findings.

PIC typically presents in 20- to 40-year-old myopic women. Although our patient was emmetropic, she was found to have this condition in her late 20s and experienced complications in her late 30s. In a 2007 survey, 26% of PIC patients surveyed reported a family history of autoimmune diseases including systemic lupus erythematosus, which our patient had in her family history (Radgonde et al.). There is a possible genetic connection of autoimmune disease, which includes the patient’s scleroderma morphea, and inflammatory conditions such as the white dot syndromes.

Marisa Asheim

Evaluation

A diagnosis of PIC is based on clinical findings with a bilateral presentation of multiple small, discrete, yellow or white spots in the fundus with little or no intraocular inflammation. Fluorescein angiography will show early hyperfluorescence and late staining of the lesions. As the lesions resolve over the course of several weeks, they may leave atrophic chorioretinal scars.

Leonid Skorin Jr.

Choroidal neovascular membranes (CNVMs) and resultant serous retinal detachments or edema can occur in 40% of patients, usually over subretinal scars (Radgonde et al.). Patients have an increased risk of developing CNVM with the presence of CNVM in the fellow eye. Our patient’s presentation was different in that the subfoveal CNVM occurred with an active lesion rather than an atrophic scar.

Differential diagnosis

Several systemic conditions should be considered as differential diagnoses with PIC and were ruled out in her initial exam. These include presumed ocular histoplasmosis, sarcoidosis, myopic degeneration maculopathy, infectious etiologies (viral, bacterial, fungal, protozoan and helminthic), other white dot syndromes and neoplasm.

Treatment

Typically, no treatment of PIC is needed because the lesions tend to be self-limiting. In the case of subfoveal CNVM, photodynamic therapy (PDT) can be used, or intravitreal anti-VEGF agents are indicated as experimental treatment. For juxtafoveal or extrafoveal CNVM, focal laser photocoagulation should be considered. There is evidence suggesting intravitreal anti-VEGF injections of 1.25 mg bevacizumab can result in stabilization or improvement of vision and reduction of macular edema for both subfoveal and juxtafoveal CNVM (Zhang et al.). Treatment with steroids is controversial, but oral or intravitreal corticosteroid may be added if no improvement is found with anti-VEGF treatment alone. Intravitreal bevacizumab and dexamethasone treatments may encourage longer periods of stability and prevent severe fibrosis.

Prognosis

Macular OCT of the right eye 4 weeks after initial anti-VEGF injection

The prognosis of PIC depends on whether CNVM develops. If no CNVM occurs, visual acuity typically is 20/40 or better. If CNVM threatens the fovea, significant vision loss can result.

Case outcome

Our patient received a 1.25-mg bevacizumab intravitreal injection in her right eye at her visit to the retina specialist. At her 4-week follow-up visit with the retina specialist, her visual acuity in the right eye had improved from 20/60 to 20/30-2. OCT showed reduction in the inflammatory component of the lesions. There was persistent subfoveal fluid of the right eye on OCT, so another 1.25-mg bevacizumab intravitreal injection was performed.

Two weeks later, her visual acuity had improved by one line, to 20/25-2 OD and 20/20 OS. Oral corticosteroid treatment was discussed as an option if intravitreal anti-VEGF treatment did not provide any further improvement in visual acuity going forward. In our patient, oral corticosteroids would be preferred over intravitreal dexamethasone because she is phakic and has a clear natural lens. Intravitreal corticosteroids have a propensity to accelerate cataract formation.

Other white dot syndromes

Other white dot syndromes may look similar to PIC, and none more so than multifocal choroiditis (MFC) with panuveitis. It is thought that these are variations of the same condition, with MFC having a more inflammatory presentation.

MFC typically presents in 20- to 60-year-old healthy Caucasian women. The presentation is similar to PIC, with multiple yellow or gray lesions in the fundus that show early hyperfluorescence and late staining of the lesions. MFC will show more anterior chamber inflammation and vitritis than PIC and may respond better to corticosteroid treatment.

PAGE BREAK

Birdshot retinochoroidopathy occurs in an older population than most of the white dot syndromes, with 40- to 60-year-old Caucasian women being the most commonly affected. This condition has a strong association with HLA-A29. The fundus will have multiple small, scattered, ill-defined, creamy yellow spots on the retina. Birdshot retinochoroidopathy almost always presents with moderate vitritis and no anterior chamber inflammation. The prognosis is variable because the condition is progressive, and in the later stages arteriolar narrowing, macular edema and CNVM can occur.

Serpiginous choroiditis affects men and women equally and occurs in 30- to 60-year-olds. This bilateral condition will show geographic gray-white lesions that begin either near the macula or the peripapillary region and resemble jigsaw puzzle pieces in shape. These lesions will heal into atrophic scars and result in loss of the retinal pigment epithelium, choriocapillaris and choroid. Active lesions are associated with subretinal fluid and are usually adjacent to older, atrophic scars. This disease is progressive and can lead to eventual CNVM and subsequent retinal detachment.

Multiple evanescent white dot syndrome (MEWDS) typically occurs in 20- to 30-year-old females after a viral prodrome. It presents as a granular appearance to the fovea and multiple small, discrete, white lesions of the retinal pigment epithelium. MEWDS may also present with an afferent pupillary defect, vitritis, optic disc edema, paracentral scotoma, central scotoma or an enlarged blind spot. Fundus autofluorescence will show early hyperfluorescence in a wreath-like pattern followed by late staining. Most spontaneously resolve and experience vision improvement in 7 to 10 weeks.

Acute posterior multifocal placoid pigment epitheliopathy occurs equally in males and females between the ages of 20 and 50 years. There is a strong association with HLA-B7 and HLA-DR2. This condition presents bilaterally with large, yellow-white geographic lesions that scar and atrophy over 1 to 2 weeks. Fundus autofluorescence will show early hypofluorescence and late staining of placoid lesions. No treatment is necessary, but corticosteroids may be used if sight-threatening lesions occur.

Disclosures: Asheim and Skorin report no relevant financial disclosures.