Major reviewPunctate inner choroidopathy: A review
Introduction
Punctate inner choroidopathy (PIC) is a relatively rare idiopathic inflammatory multifocal chorioretinopathy that most commonly affects young myopic women. Most of these lesions involve the posterior pole, arising at the level of the retinal pigment epithelium (RPE) and inner choroid in the absence of anterior chamber or vitreous inflammation (Fig. 1).86 Although it may be self-limiting with a favorable outcome, inflammation or neovascularization abutting the fovea may cause permanent visual loss. Depending on the course of disease and development of complications, treatment may range from observation to systemic immunosuppression and intravitreal antiangiogenic therapies.
PIC was first described by Watzke and colleagues in 1984 in a series of 10 young, otherwise healthy myopic women who presented with blurred central vision, photopsia, and paracentral scotomas and had well circumscribed yellow-gray lesions at the level of the inner choroid and retinal pigment epithelium associated with small neurosensory retinal detachments in the macula in the absence of detectable intraocular inflammation.86 Eight of the 10 patients presented with bilateral lesions, and choroidal neovascularization (CNV) developed in 6 patients. Although initially hypothesized to be secondary to myopia, the episodic nature of recurrences was subsequently acknowledged to be more suggestive of an underlying inflammatory pathogenesis.1
Punctate inner choroiditis, multifocal inner choroiditis.
Section snippets
Epidemiology and demographics
PIC is a relatively rare multifocal chorioretinopathy. It is difficult to make an accurate estimate of the incidence and prevalence of PIC for a number of reasons: first, there is a wide range of presentation and severity, such that many cases may remain unrecognized; second, there is uncertainty over its classification, notably whether it is a distinct entity from multifocal choroiditis with panuveitis (MCP) or part of the same spectrum; and third, in the absence of national registries or
Pathogenesis
The etiology of PIC is unknown, and its pathogenesis poorly understood. In common with the other inflammatory conditions that have been lumped together as “white dot syndromes,” it is proposed to be an autoimmune disease that arises in the context of polygenic susceptibility triggered by an environmental stimulus, such as infection, immunization, or stress. In the context of PIC, a plausible mechanism should ideally also explain the preponderance (but not exclusivity) of the female myopic
Clinical description
According to the survey by Gerstenblith and colleagues, initial symptoms in PIC are most commonly scotoma (91%), blurred vision (86%), photopsia (73%), floaters (69%), photophobia (69%), and metamorphopsia (65%). Loss of peripheral vision was reported in 26% of patients.30 These symptoms may fluctuate in severity, with 32% reporting symptoms waxing and waning before commencing treatment. Visual acuity at presentation is variable, reflecting the variable location of inflammatory lesions or their
Ancillary tests
Investigations used in diagnosing and monitoring PIC have mainly included fluorescein angiography, indocyanine green angiography, and OCT although newer modalities like fundus autofluorescence (FAF) imaging and OCT angiography are proving useful (Fig. 2, Fig. 3, Fig. 4).32, 40, 51, 79, 87, 90
The arteriovenous phase of fluorescein angiography shows punctate hyperfluorescent choroidal lesions with or without CNV. Areas of hyperfluorescence corresponding to the lesions will continue to persist
Management
The management of PIC is challenging for a number of reasons. First, the variable severity of disease between patients (or even in the same patient at different times) may mean that optimal treatment may appropriately range from observation to intensive immunosuppression or intravitreal anti-VEGF therapy. Second, any treatment strategy should distinguish between the major causes of sight loss in PIC. In pathogenetic terms, new or worsening PIC lesions are likely to reflect active inflammation,
PIC and pregnancy
Pregnancy has been associated with the development or recurrence of CNV, being reported secondary to PIC, POHS, or even in the absence of preexisting inflammation.66, 76 It is likely that this arises from elevated levels of angiogenic factors such as VEGF and placental growth factor. VEGF levels increase during the first trimester and then decline,50 whereas placental growth factor increases steadily throughout pregnancy.42
Many immune conditions improve during pregnancy as a result of
Prognosis
The visual outcome in PIC depends on the location of the lesions and whether they are complicated by the formation of CNV. Many patients do well, with visual acuity of 20/40 or better; however, approximately one-fifth will end up with a VA of <20/200 mainly from development of CNV and subretinal fibrosis.10, 59, 86 The risk of CNV is higher in PIC than other posterior and panuveitic conditions. The presence of active inflammation and previous CNV in the other eye increase the risk.6, 30, 62 The
Further research and patient engagement
Despite the advances in imaging that enable unparalleled visualization of the onset and development of PIC lesions, the etiology of PIC remains unknown, the indications for treatment are uncertain, and high-level evidence to support a treatment strategy is lacking. As discussed earlier, conducting randomized controlled trials of treatments for PIC is challenging; however, there is a need for this higher level evidence. We would urge the community of clinical experts and patients to work
Conclusions
In summary, PIC is a relatively rare, idiopathic inflammatory multifocal chorioretinopathy with a variable outcome ranging from complete spontaneous recovery to bilateral severe visual loss. Detection and monitoring have been greatly facilitated by modern scanning techniques, especially OCT and autofluorescence imaging, and may be enhanced by coregistration of sequential images to detect change over time. Our concern, however, is that even with these advances, there are many occasions when this
Method of literature search
The original literature search was undertaken in January 2016, with an updated search conducted in May 2016 to identify any “late-breaking” articles. The following databases were searched: Medline, EMBASE, and the Cochrane Library with a date limit of 1946 to the present for Medline, 1974 to present for EMBASE, and no date restriction for Cochrane. The search used the following terms: “Punctate inner choroidopathy,” “Punctate inner choroiditis,” and “multifocal inner choroiditis.” Papers were
Disclosures
The authors declare no conflicts of interest.
Acknowledgments
Pearse A. Keane has received a proportion of his funding from the Department of Health's NIHR Biomedical Research Centre for Ophthalmology at Moorfields Eye Hospital and UCL Institute of Ophthalmology. The views expressed in the publication are those of the author and not necessarily those of the Department of Health.
References (90)
- et al.
Punctate inner choroidopathy
Surv Ophthalmol
(2011) - et al.
Risk of choroidal neovascularization among the uveitides
Am J Ophthalmol
(2013) - et al.
The prevalence of HLA-B7 in presumed ocular histoplasmosis
Am J Ophthalmol
(1978) - et al.
Visual prognosis of multifocal choroiditis, punctate inner choroidopathy, and the diffuse subretinal fibrosis syndrome
Ophthalmology
(1996) - et al.
Comparison of antimetabolite drugs as corticosteroid-sparing therapy for noninfectious ocular inflammation
Ophthalmology
(2008) - et al.
Evaluation of the progression rate of atrophy lesions in punctate inner choroidopathy (PIC) based on autofluorescence analysis
Photodiagnosis Photodyn Ther
(2014) - et al.
Recurrence of a choroidal neovascular membrane in a patient with punctate inner choroidopathy treated with daily doses of thalidomide
Am J Ophthalmol
(1996) - et al.
White spot syndromes of the retina: a hypothesis based on the common genetic hypothesis of autoimmune/inflammatory disease
Am J Ophthalmol
(2003) - et al.
Randomized comparison of systemic anti-inflammatory therapy versus fluocinolone acetonide implant for intermediate, posterior, and panuveitis: the multicenter uveitis steroid treatment trial. Multicenter Uveitis Steroid Treatment (MUST) Trial Research Group
Ophthalmology
(2011) - et al.
Focal choroidal excavation in multifocal choroiditis and punctate inner choroidopathy
Ophthalmology
(2015)
Intravitreal ranibizumab in the treatment of choroidal neovascular membrane secondary to punctate inner choroidopathy
Can J Ophthalmol
Punctate inner choroidopathy: resolution after oral steroid treatment and review of the literature
Can J Ophthalmol
Long-term visual outcomes of intravitreal bevacizumab in inflammatory ocular neovascularization
Am J Ophthalmol
The prevalence of HLA-B7 in presumed ocular histoplasmosis in patients with peripheral atrophic scars
Am J Ophthalmol
Subfoveal choroidal neovascularization in punctate inner choroidopathy. Surgical management and pathologic findings
Ophthalmology
Enlarged blind spots in chorioretinal inflammatory disorders
Ophthalmology
Photodynamic therapy of idiopathic and inflammatory choroidal neovascularization in young adults
Ophthalmology
Birdshot retinochoroidopathy
Am J Ophthalmol
Acute posterior multifocal placoid pigment epitheliopathy
Am J Ophthalmol
Birdshot chorioretinopathy
Surv Ophthalmol
Intravitreal ranibizumab (Lucentis®) in the treatment of choroidal neovascular membrane secondary to punctate inner choroidopathy
Arch Soc Esp Oftalmol
Punctate inner choroidopathy
Am J Ophthalmol
Characterization of punctate inner choroidopathy using enhanced depth imaging optical coherence tomography
Ophthalmology
Spectral-domain optical coherence tomographic findings at each stage of punctate inner choroidopathy
Ophthalmology
Punctate inner choroidopathy and multifocal choroiditis with panuveitis share haplotypic associations with IL10 and TNF loci
Invest Ophthalmol Vis Sci
Cytokine polymorphism in noninfectious uveitis
Invest Ophthalmol Vis Sci
Circumpapillary chorioretinopathy in multiple evanescent white-dot syndrome
Retina
Development and validation of quality-of-life questionnaires for birdshot chorioretinopathy
Ophthalmology
Unilateral punctate inner choroidopathy with choroidal neovascular membrane in a young male
Indian J Ophthalmol
Choroidal neovascularization due to punctate inner choroidopathy: long-term follow-up and review of literature
Clin Ophthalmol
Resolution of punctate inner choroidopathy lesions with oral prednisone therapy
Arch Ophthalmol
Peripapillary subretinal fibrosis: a characteristic finding of multifocal choroiditis and panuveitis
Retina
Combined photodynamic therapy and intravitreal triamcinolone for choroidal neovascularization secondary to punctate inner choroidopathy or of idiopathic origin: one-year results of a prospective series
Retina
Intravitreal bevacizumab (avastin) for choroidal neovascularization secondary to central serous chorioretinopathy, secondary to punctate inner choroidopathy, or of idiopathic origin
Am J Ophthalmol
Characterization of macular lesions in punctate inner choroidopathy with spectral domain optical coherence tomography
J Ophthalmic Inflamm Infect
Photodynamic therapy: a treatment option in choroidal neovascularization secondary to punctate inner choroidopathy
Br J Ophthalmol
Resolution of activity (choroiditis and choroidal neovascularization) of chronic recurrent punctate inner choroidopathy after treatment with interferon B-1A
Retina
Presumed ocular histoplasmosis syndrome: update on epidemiology, pathogenesis, and photodynamic, antiangiogenic, and surgical therapies
Curr Opin Ophthalmol
Photodynamic therapy for subfoveal and juxtafoveal choroidal neovascularization associated with punctate inner choroidopathy
Ocul Immunol Inflamm
Visual and optical coherence tomography outcomes of intravitreal bevacizumab and ranibizumab in inflammatory choroidal neovascularization secondary to punctate inner choroidopathy
Eur J Ophthalmol
Mycophenolate mofetil for ocular inflammation
Am J Ophthalmol
Treatment of non-age-related macular degeneration submacular diseases with macular translocation surgery
Retina
Two-year results of surgical removal of choroidal neovascular membranes related to non-age-related macular degeneration
Br J Ophthalmol
Punctate inner choroidopathy: clinical features and outcomes
Arch Ophthalmol
Idiopathic multifocal choroiditis: a comment on present and past nomenclature
Retina
Cited by (62)
Punctate inner choroidopathy: A review of the current diagnostic and therapeutic approaches
2024, Progress in Retinal and Eye ResearchPunctate Inner Choroiditis
2024, Advances in Ophthalmology and OptometryExploring Imaging Characteristics Associated With Disease Activity in Idiopathic Multifocal Choroiditis: A Multimodal Imaging Approach
2023, American Journal of OphthalmologyStepwise approach for fundus imaging in the diagnosis and management of posterior uveitis
2023, Survey of Ophthalmology
- 1
Contributed equally to this work and share the role of first author.