White Dot Syndrome Series Part 3: Punctate Inner Choroidopathy

Slideshow

  • Figure 1. A) Small (punctate) yellowish-white lesions in the maculae. B) Optical coherence tomography (OCT) of the right eye shows a foveal area of choroidal excavation (red circle). C) OCT of the left eye shows thickening of the retinal pigment epithelium, choroid and subfoveal serous detachment. D) On fundus autofluorescence (FAF), the lesions appear as small areas of hypo-autofluorescence.

  • Figure 2. A) This fundus photo, FAF, and OCT image show a patient with PIC. B) In these fluorescein angiography images, small hyperfluorescence lesions can be seen in the macula and nasal to disc area. C) On indocyanine green, these lesions block the choroid and appear as hyperfluorescent areas.

  • Figure 3. A) The difference of choroidal thickness is noted in the active phase. B) This image demonstrates an improved disease state following intravitreal steroid therapy.

  • Figure 4. Advancing disease results in not only choroidal neovascularization, but also scars associated with the inflammatory lesions.

White Dot Syndromes are idiopathic inflammatory findings characterized by white lesions across the retinal pigment epithelium or outer retina. Optometry Advisor’s multipart White Dot Syndrome Series details how to elucidate a diagnosis based on the imaging of these lesions.

Punctate inner choroidopathy (PIC) is an inflammatory disease affecting the choroid and outer retina that can be classified as a white dot syndrome

The condition was first reported in 1984 when a case series of 10 patients (100% women) with moderate myopia presented with blurred vision, photopsia, and paracentral scotomas. The clinical team behind the study described small yellow-white lesions of the inner choroid and the retina pigment epithelium (RPE) with overlying serous detachment which, in the acute phase, leaked fluorescein. With time, the lesions became atrophic and pigmented. Choroidal neovascular membranes (CNVM) later developed in 6 of the 10 patients. Since that initial report, not much has changed in the demographic and associated findings, except for the advent of optical coherence tomography (OCT), and fundus autofluorescence (FAF), which have given clinicians a better understanding of the condition and its clinical course (Figures 1 and 2). 

PIC vs POHS

The underlying pathophysiology of PIC is not well understood. One research group hypothesized that an immune or inflammatory response in the choroid and the outer retina against an unknown offender results in the formation of these lesions.2 Parallel tissue response has been made between PIC and presumed ocular histoplasmosis (POHS), which results in similar clinical presentations.2 This causes a conundrum in differential diagnosis of these 2 conditions.3

Imaging Options

PIC lesions can present on OCT in various ways, depending on the phase of the disease. Acute inflammation may cause a subretinal elevation of the RPE. Serous detachments may be observed on OCT. Older lesions result in scarring of the RPE and outer retina and can even result in choroidal excavations. OCT with enhanced depth imaging (EDI-OCT) or swept source OCT (SS-OCT) may be used to better visualize the choroid with reports of increased choroidal thickness during active phases of inflammation (Figures 1 and 3).4-6

FAF is beneficial in monitoring lesions for longer periods of time, and may show a greater extent of lesions than are typically visible on clinical examination. In general, newer, active lesions present as hyper-autofluorescence, with older inactive lesions appearing as hypo-autofluorescence (Figures 1 and 2).4-6

PIC Patients

The incidence of PIC is approximately 13.5% among posterior uveitic conditions. The clinical findings of PIC are specific and consistent making them relatively easy for detection by artificial intelligence. These include “punctate” lesions smaller than 250 µm in the posterior pole and possibly midperiphery with, absent or minimal anterior chamber and vitreous cells.4 

The consensus regarding the demography and symptomatology of PIC indicates that the disease affects young women who have myopia. Symptoms include scotoma, blurred vision, photopsias, floaters, photophobia, metamorphopsia, and loss of peripheral vision.5-8 

Most patients with PIC have good visual outcomes of 20/40 or better, although long-term vision loss is possible.9 PIC can lead to vision loss in 2 different ways. First, inflammatory PIC lesions that lead to subfoveal scarring cause vision loss by disruption of the RPE and photoreceptors (Figure 4). Second, patients with PIC are at high risk for choroidal neovascularization. Research shows that up to 75% of patients with PIC develop CNV.8-10 

Management Techniques

Treatment outcomes are often favorable and may include immunosuppressive agents, such as corticosteroid (systemic or local routes, such as periorbital and intravitreal), as well as systemic immunomodulatory drugs.8,9 Patients treated with immunomodulatory drugs may have a slightly reduced chance of CNV recurrence.9 Treatment of CNV associated with PIC with anti-vascular endothelial growth factor (VEGF) drugs is also well tolerated and effective.

Although PIC is not a common condition, it should be considered as a differential diagnosis in patients presenting with “white dot” lesions. Proper management of PIC can reduce visual loss associated with this condition. 

References

  1. Watzke RC, Packer AJ, Folk JC, Benson WE, Burgess D, Ober RR. Punctate inner choroidopathy. Am J Ophthalmol. 1984;98(5):572-584. doi:10.1016/0002-9394(84)90243-5. 
  2. Jampol LM, Becker KG. White spot syndromes of the retina: a hypothesis based on the common genetic hypothesis of autoimmune/inflammatory disease. Am J Ophthalmol. 2003;135:376-379. doi:10.1016/s0002-9394(02)02088-3
  3. Diaz RI, Sigler EJ, Rafieetary MR, Calzada JI. Ocular histoplasmosis syndrome. Surv Ophthalmol. 2015;60(4):279-295. doi:10.1016/j.survophthal.2015.02.005.
  4. Standardization of Uveitis Nomenclature (SUN) Working Group. Classification criteria for punctate inner choroiditis. Am J Ophthalmol. 2021;228(4):275-280. doi:10.1016/j.ajo.2021.03.046. 
  5. Gerstenblith AT, Thorne JE, Sobrin L, et al. Punctate inner choroidopathy: a survey analysis of 77 persons. Ophthalmol. 2007;114(6):1201-1204. doi:10.1016/j.ophtha.2006.10.047
  6. Essex RW, Wong J, Fraser-Bell S, et al. Punctate inner choroidopathy: clinical features and outcomesArch Ophthalmol. 2010;128(8):982-987 doi:10.1001/archophthalmol.2010.157
  7. Brown J, Folk JC, Reddy CV, Kimura AE. Visual prognosis of multifocal choroiditis, punctate inner choroidopathy, and the diffuse subretinal fibrosis syndromeOphthalmol. 1996;103(7):1100–1105. doi:10.1016/S0161-6420(96)30561-7
  8. Campos J, Campos A, Mendes S, et al. Punctate inner choroidopathy: a systematic review. Med Hypothesis Discov Innov Ophthalmol. 2014;3(3):76-82.
  9. Leung TG, Moradi A, Liu D, et al. Clinical features and incidence rate of ocular complications in punctate inner choroidopathy. Retina. 2014;34(8):1666-1674. doi:10.1097/IAE.0000000000000125
  10. Patel KH, Birnbaum AD, Tessler HH, Goldstein DA. Presentation and outcome of patients with punctate inner choroidopathy at a tertiary referral center. Retina. 2011;31(7):1387-1391. doi:10.1097/IAE.0b013e3182069a8f