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Patient presents with long history of uveitis
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A 46-year-old female Alaskan Native who was being followed for uveitic glaucoma presented to the clinic for a 30-2 threshold visual field, an optical coherence tomography scan of the retinal nerve fiber layer and an IOP check. The patient stated that she was concerned about a “white haze” in her vision that she had been noticing for the past few weeks in both eyes. She denied any pain or discomfort.
The patient had a history of chronic panuveitis with secondary glaucoma. She had been treated with topical glaucoma medications for more than 20 years. Her current ocular medications included 0.5% timolol and Travatan Z (travoprost ophthalmic solution 0.004%, Alcon), one drop of each instilled in both eyes at bedtime. Ocular surgeries include cataract extraction 10 years prior. Her systemic history was noncontributory.
Visual acuities were hand motion in the right eye and 20/30- in the left, with no improvement on pinhole. Extraocular movements were full with no diplopia in any field of gaze. Pupils were both nonresponsive and fixed at 2 mm OD and 8 mm OS. Goldmann applanation tonometry was 28 mm Hg OD and 20 mm Hg OS. Slit lamp examination revealed 3+ scattered granulomatous (mutton-fat) keratic precipitates concentrated inferiorly on the corneal endothelium in the right eye. The cornea in the left eye was clear. There was also an anterior chamber reaction in both eyes with 3+ cells and flare, spilling into the anterior vitreous of the left eye.
Ross F. English
The patient had posterior synechiae nearly 360⁰ in the right eye with extensive fibrosis on the anterior lens surface. She was pseudophakic in the left eye. The posterior chamber IOL was stable and its posterior capsule clear. Cells were also visible in the posterior vitreous of the left eye.
Fibrosis of the right lens prevented any posterior view. Fundus examination of the left eye revealed a multiple areas of retinal pigment epithelium (RPE) mottling and atrophy, as well as round, white, chorioretinal lesions in the midperiphery. Macular OCT confirmed foveola integrity with no edema or thickening. Areas of scattered RPE dropout were visible in the perifoveal area. An OCT of the retinal nerve fiber layer showed longstanding thinning superior and inferior with no apparent progression.
Anterior segment photo of the right eye.
Images: English RF
Anterior segment photo of the left eye.
The differential diagnosis included Vogt-Harada (VKH) syndrome, sympathetic ophthalmia, sarcoidosis and tuberculosis.
This patient had been diagnosed with Harada’s disease about 15 years prior. Harada’s disease refers to VKH syndrome in the absence of systemic manifestations. VKH is a rare disease that affects approximately three out of 1 million people in the U.S. It affects women more commonly than men, is typically found in patients between ages 30 and 60, and is most prevalent in those of Asian, Hispanic, Native American and Middle Eastern descent. It is much less common in Caucasians and Africans.
Description
VKH syndrome gets its name from three individuals who originally published research on the syndrome independently. It is an inflammatory disorder, hypothesized to be mediated by T-cells, and characterized by panuveitis and serous retinal detachments. It also affects the neurological and cutaneous systems, causing neck stiffness, headaches, hearing loss, alopecia, vitiligo and poliosis.
To meet the criteria of true VKH syndrome the patient must have three of the following signs with no history of any ocular trauma or surgery: chronic bilateral iritis, posterior uveitis, neurological signs or symptoms, and cutaneous signs. If only ocular signs are present, then the disease is known as Harada’s disease. Harada’s disease should not be confused with sympathetic ophthalmia, which is a bilateral granulomatous uveitis secondary to accidental or surgical injury to the uvea of one eye.
Anterior ocular signs of VKH syndrome include an anterior chamber inflammatory reaction characterized by granulomatous keratic precipitates. Peripheral anterior and posterior synechiae as well as Koeppe and Busacca nodules on the iris can also be present. With extended inflammation, the limbus can become depigmented (Sugiura sign), as can the ciliary body. Posterior inflammation is characterized with multiple areas of serous retinal detachments, choroidal neovascularization and Dalen-Fuch’s nodules. Dalen-Fuch’s nodules are made up primarily of macrophages located beneath the RPE and appear as indistinct round, white lesions less than 1 disc diameter in size. Optic disc edema and hyperemia eventually lead to disc pallor. With time, the retinal detachments cause the RPE to mottle and atrophy. This is known as a “sunset fundus.”
Staging
VKH syndrome is classified into four different stages: prodromal, uveitic, convalescent and chronic. The prodromal stage is characterized by the neurological signs mentioned above, as well as confusion, convulsions, cranial nerve palsies, optic neuritis and tinnitus. A lumbar puncture may also reveal an increase in lymphocytes, but only in the prodromal phase. This stage lasts anywhere from a few days to a few weeks and will be followed by the uveitic stage.
In the uveitic stage, patients will often present to their eye care provider with eye pain and blurred vision. The hallmark finding during this stage is the multiple focal areas of retinal detachments. Choroiditis and a granulomatous uveitis are usually present as well. Ciliary edema can also occur.
The third stage, the convalescent stage, occurs after the uveitis and swelling have subsided. The sequelae of the inflammation are a sunset fundus and Dalen-Fuch’s nodules. Cutaneous findings will also occur during this time. It can last anywhere from months to years, until it is interrupted by the chronic stage.
The chronic stage typically manifests as an anterior uveitis without posterior involvement. The chronic stage occurs in approximately 50% of patients within 6 months of the convalescent stage. This stage is highly associated with neovascularization, synechiae, cataracts and glaucoma.
Optical section of the right cornea after 1 week of topical treatment, showing a large
improvement in the number of granulomatous keratic precipitates.
Fundus photo collage shows classic sunset fundus and Dalen-Fuchs nodules of the left eye
after 1 week of topical treatment.
Management
Topical steroids are the treatment of choice for anterior uveitis, with the dose depending on the severity. A cycloplegic agent may also be used to control pain and reduce adhesions. In cases of panuveitis, oral steroids are often needed to control the inflammation. Dosing is usually 1 mg/kg/d to 2 mg/kg/d of prednisone with a typical taper of 6 months. If the patient cannot tolerate oral steroids, another immunosuppressive, such a cyclosporine, can be used. The patient should be referred to his or her primary care physician or a neurologist for treatment of any other systemic manifestations.
Our patient, whose pathology was confined to ocular structures, was initially treated with Durezol (difluprednate 0.05%, Alcon) dosed every 2 hours and fluorometholone ointment at bedtime. Atropine 1.0% was also prescribed for use daily. She was told to continue her timolol and Travatan Z at bedtime. She refused oral steroids because she was not able to tolerate the side effects when previously placed on them. A 1-week follow up was scheduled.
Macular OCT of the left eye.
RNFL OCT of the left eye.
At her follow up visit, the patient reported that the “white haze” in her vision had nearly resolved. Again, she reported no pain or discomfort. The inflammation had subsided from the previous visit to 1+ cells in the anterior chamber of both eyes, with 1+ cells in the anterior vitreous of the left eye. Minimal granulomatous keratic precipitates persisted on the corneal endothelium of the right eye. The visual acuity had also improved to 20/150 OD and remained 20/30- OS.
It was also seen during this same visit that the patient had developed a steroid response with IOPs measured at 58 mm Hg OD and 57 mm Hg OS. Gonioscopic viewing confirmed her angles were open. In-office use of timolol and brimonidine, alternated every 15 minutes, reestablished IOPs to 28 mm Hg OD and 29 mm Hg OS over the course of 2 hours. Following IOP recovery, timolol, brimonidine and Durezol were prescribed four times a day. She was told to discontinue the Travatan Z, atropine and fluorometholone ointment and return to the clinic the next day.
At her appointment the following day, the patient’s IOPs were 19 mm Hg OD and 16 mm Hg OS. The uveitis signs were essentially unchanged. She was told to continue the Durezol four times a day, as well as both the timolol and brimonidine three times a day.
One week later, the episode of inflammation had completely remitted, with only signs of longstanding inflammatory damage remaining. Visual acuities remained 20/150 OD and 20/30 OS. The patient was instructed to continue dosing both ocular hypotensives three times per day and slow-taper the Durezol. Following the taper, she was referred to ophthalmology to have the posterior synechiae surgically broken and phacoemulsification with IOL implantation in the right eye.
Discussion
Brimonidine’s potential for tachyphylaxis, while uncertain, has been shown to be lower than that of apraclonidine. The use of prostaglandin therapy is controversial, as some reports indicate a mechanistic increase of inflammation. However, as Goldstein and colleagues report, the majority of glaucoma arising from angle blockage secondary to inflammatory cells resolves after a few days of steroid therapy.
Other retrospective control studies demonstrate that prostaglandins are an effective method of lowering IOP in uveitic glaucoma and have no increased likelihood of exacerbating anterior uveitis or cystoid macular edema (CME). Likewise, according to Schumer and colleagues, chemotaxsis has not been demonstrated in clinical trials to increase with prostaglandin use. For these reasons, while the risk is minimal and no CME was present, the authors decided to switch the patient’s form of ocular hypotensive.