|Year : 2016 | Volume
| Issue : 2 | Page : 96-102
Inflammatory macular diseases: A review
Dheeresh K Velly1, Haard Shah2, Ranju Kharel3, Jyotirmay Biswas4
1 Medical Retina, Malabar Superspeciality Eye Hospital, Veepes Space, Calicut, Kerala, India
2 Vitreo Retina, Shri Bhagwan Mahavir Vitreo-retinal Services, Sankara Nethralaya, Chennai, Tamil Nadu, India
3 B. P. Koirala Lions Centre for Ophthalmic Studies, Tribhuvan University, Institute of Medicine, Kathmandu, Nepal
4 Department of Ocular Pathology, Medical and Vision Research Foundations, Sankara Nethralaya, Chennai, Tamil Nadu, India
|Date of Web Publication||20-Mar-2017|
Dheeresh K Velly
Malabar Superspeciality Eye Hospital, Veepes Space, Calicut, Kerala
Source of Support: None, Conflict of Interest: None
Inflammatory macular diseases, a group of disorders, are a major cause of severe visual impairment. They may be caused by primary ocular disease or secondary to systemic or infectious disease. All of them present with almost similar symptoms. The key to successful management is early detection and aggressive treatment with steroids, antimicrobials, and if needed, immunosuppressives. Risk of recurrences and complications, such as choroidal neovascularization, are taken in to account in the management.
Keywords: Choroiditis, granuloma, uveitis, vitritis
|How to cite this article:|
Velly DK, Shah H, Kharel R, Biswas J. Inflammatory macular diseases: A review. Kerala J Ophthalmol 2016;28:96-102
| Introduction|| |
Inflammatory macular diseases (IMD) are conditions characterized by inflammation primarily involving the macula either at the level of retinal pigment epithelium (RPE), outer retina, or choroid. Because the central vision is compromised, it is important to diagnose and treat them early. Based on the etiology, IMD can be either infectious or noninfectious [Table 1].
Infectious inflammatory macular diseases
It is caused by the infection by an intracellular protozoan Toxoplasma Gondii. It may occur either in a congenital or postnatal acquired form. It is unilateral in 60% of the cases.
Symptoms: The most common symptoms of active ocular toxoplasmosis are blurring or decrease in vision and floaters.
Signs: The hallmark of the disease is a necrotizing retinochoroiditis [Figure 1], satellite lesion adjacent to old hyperpigmented scars accompanied by vitreous inflammation [Figure 2], and anterior uveitis. Sometimes retinal vasculitis is also present. Macular involvement occurs in 50% of the cases. It appears as a cicatricial lesion with radial disposition of pigments around a central necrotic zone. Toxoplasma presenting as serous macular detachment has been reported.
Diagnosis: In most cases, diagnosis is made clinically. Serological detection of IgG and IgM by enzyme-linked immunosorbent assay (ELISA) test helps in the diagnosis. Polymerase chain reaction (PCR) may be useful in patients who present with atypical features, the elderly, and those who are immunocompromised.
Treatment: It involves a course of systemic antiparasitic drugs with the use of systemic corticosteroids after 48 hours. Treatment is given for 4–8 weeks depending upon the severity of the disease. The drugs used include pyrimethamine, spiramycin, sulfadiazine, azithromycin, clindamycin, and atovaquone.
Periocular corticosteroids are contraindicated. In pregnancy, intravitreal clindamycin and dexamethasone can be given. Periodic evaluation of the retina is mandatory as the disease is recurrent with new lesions occurring at the margins of old lesions as well as elsewhere in the fundus.
Complications: Choroidal neovasularization (CNV), serous macular detachment, and macular edema have to be treated accordingly.
Toxocariasis is an infection caused by dog round worm Toxocara canis and less frequently by cat round worm Toxocara cati. Based on the ophthalmological findings, ocular toxocariasis can be classified into peripheral granuloma, posterior pole granuloma, chronic endophthalmitis.
Posterior pole granuloma: Patients presents with unilateral visual impairment. Clinically, it appears as a large white or grey spherical intraretinal or subretinal granuloma [Figure 3]. Active disease has intense vitritis. With cicatricial granuloma the vitreous reaction is less. Perilesional retina can show hyperpigmentation of retinal pigment epithelium (RPE) and wrinkling of inner limiting membrane (ILM). Macular lesion may be seen in association with peripheral inflammatory masses.
Diagnosis: Clinical presentation of localized granuloma in the periphery and posterior pole are very typical. Serum ELISA for Toxocara confirms the diagnosis.
CNV may occur as a late complication. Posterior granuloma can mimic retinoblastoma endophthalmitis, toxoplasmosis, and coats disease.
Treatment: Antihelminthic drugs used are albendazole, thiabendazole, and diethylcarbamazine along with topical and systemic steroids.
Tuberculosis (TB) is a chronic granulomatous infection caused by the tubercle bacillus Mycobacterium tuberculosis. Ocular manifestation of TB may be due to either an active infection or an immunological reaction to the organism. Primary ocular TB is defined as one in which eye is the primary portal of entry. Secondary ocular TB, which is the most common manifestation, occurs by hematogenous spread of organisms or by contiguous spread from adjacent structures.
Focal, or less frequently, multifocal choroiditis is characterized by deep discrete yellow lesion between 0.5 mm and 3 mm in diameter predominantly located in the posterior pole. The lesions are typically elevated and may be accompanied by serous retinal detachment. Exudative hemorrhagic periphlebitis in a patient with uveitis is highly suggestive of tubercular etiology.
Macular involvement can be as a single, large elevated choroidal mass, or tuberculoma [Figure 4] that varies in size from 4 mm to 14 mm and may be accompanied by neurosensory retinal detachment and macular star formation.
Diagnosis: Mantoux test, chest X-ray, HRCT chest, QuantiFERON TBGOLD test, PCR for TB. Enhance depth imaging optical coherence tomography (EDI-OCT) is suitable to visualize choroidal granuloma.
Treatment: Antitubercular drugs. Systemic and topical corticosteroids are frequently used in conjunction with antimicrobial therapy to treat the inflammatory component [Figure 4].
Noninfectious inflammatory macular diseases.
Macular geographic helicoid peripapillary choroidopathy
It is a variant form of serpiginous choroiditis, which is an uncommon, chronic, progressive recurrent bilateral disease of unknown etiology predominantly, involving the macula.
Age group\: 4–6th decade with no sex predilection.
Symptoms: Patients present early in the course of the disease with an acute onset of central vision loss. Central paracentral scotomas may be present.
Signs: Mild forms of anterior uveitis and vitritis are common. Active lesions [Figure 5]a are grey white and may remain active for many months. Inactive lesions are characterized by scalloped, atrophic areas of choroidal and RPE atrophy [Figure 5]b.
|Figure 5: (a) Active Geographic Helicoid Peripapillary Choroiditis lesion. (b) Inctive Geographic Helicoid Peripapillary Choroiditis lesion. (c) FFA findings in active Geographic Helicoid Peripapillary Choroiditis (early hypofluorescence). (d) FFA findings in active Geographic Helicoid Peripapillary Choroiditis (late hyper fluorescence)|
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Diagnosis: Fluorescein angiography of active lesions shows early hypofluorescence and late hyperfluorescence [Figure 5]c and [Figure 5]d; inactive lesions show window defects.
Fundus autofluorescence: Hyperautofluorescence corresponding to areas of active areas.
Indocyanine green angiography (ICG): Active lesions reveal marked hypofluorescence through all phases of angiogram.
Optical coherence tomography: OCT reveals hyperreflective echoes in the outer retina with disruption of inner segment-outer segment (IS/OS) junction. There is RPE thinning.
Macular GHPC may be misdiagnosed as macular degeneration, macular dystrophies, or toxoplasmosis.
Treatment: Systemic corticosteroids are found to be effective in controlling active lesions, however, their role in preventing recurrences is doubtful. Fovea threatening cases are treated with high doses of intravenous steroids (1 g intravenous methylprednisolone (IVMP) for 3 days) followed by oral steroids and immunosuppressives. Within a few weeks, active lesion converts to inactive lesion with eventual RPE atrophy. Usage of intravitreal triamcinolone (IVTA) has been attempted successfully in cases where systemic steroids are contraindicated. Recurrences are common in macular GHPC. Immunosuppressives commonly used to treat macular GHPC are azathioprine and cyclosporine.
Clinical course: Recurrences, eventually resulting in extensive chorioretinal atrophy and sometimes with development of CNVM.
Acute posterior multifocal placoid pigment epitheliopathy
Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) is an uncommon, bilateral, idiopathic condition usually affecting both sexes equally. It is often associated with HLAB7 and HLADR2. A viral prodrome is noted in 50% of the cases.
Presentation: In the 3–4th decade.
Symptoms: Patients present with acute decrease in vision associated with photopsia, central, and paracentral scotomas.
Signs: Anterior segment is usually quiet. Minimal vitritis is present. Multiple yellowish white deep placoid lesions that typically begin at the posterior pole and then extent to the postequatorial fundus [Figure 6]. After a few days, the lesions fade centrally and are replaced by RPE disturbances. New lesions develop so that different stages of development can be seen.
|Figure 6: Yellowish white lesion in Acute Placoid Multifocal Posterior Pigmentary Epitheliopathy|
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Diagnosis: Is based on the typical clinical findings and characteristic fluorescein angiography findings.
Fundus fluorescein angiography: Early hypofluorescence corresponding to the lesion associated with nonperfusion of choriocapillaries and late hyperfluorescence caused by staining.
Optical coherence tomography (OCT): Shows increased choroidal thickness with hyperreflective echoes in the outer retina with or without localized serous detachment of retina.
Management: APMPPE has a limited clinical course with spontaneous recovery in most cases. In case of macular involvement, corticosteroids may be considered.
Poor prognostic factors in APMPPE are:
- Foveal involvement at the initial presentation
- Age greater than 60
- Unilateral presentation.
It is an uncommon bilateral usually chronic, recurrent, asymmetrical disease that predominantly affects young myopic females.
Symptoms: Presents in 3–4th decade with complaints of blurring of central vision, floaters, photopsia, metamorphopsia, and paracentral and temporal scotoma.
Signs: Multifocal choroiditis is characterized by anterior uveitis (60%) and vitritis. Yellow grey round oval lesions are seen in the outer retina and RPE [Figure 7]a. They occur in the posterior pole, peripapillary region, and midperiphery. The lesions can be arranged in clumps or linear streaks.
|Figure 7: (a) Yellow grey oval lesions in Multifocal Choroiditis. (b) FFA findings in Multifocal choroiditis- early hypofluorescence. (c) FFA findings in Multifocal choroiditis- late hyperfluorescence|
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Inactive lesions have a sharp “punched out” appearance. Peripapillary subretinal fibrosis can occur resembling a napkin holder. Cystoid macular edema (14–41%) and CNV (33%) are frequent complications leading to poor vision.,
Investigations: On fluorescein angiography, active lesions appear hypofluorescent due to blockage and late hyperfluorescent due to staining [Figure 7]b and [Figure 7]c.
OCT: RPE irregularity corresponding to a clinical lesion occurs in the active phase. IS-OS junction is often damaged.
Treatment: Aimed at inflammation and its sequelae such as CME and CNVM. Systemic and periocular steroids can be used for the treatment of macular edema. Immunomodulatory therapy is frequently required due to the chronic recurrent nature of the inflammation.
Punctate inner choroidopathy
It is an idiopathic inflammatory disorder occurring in otherwise young, healthy myopic females (90%). Mean age of presentation is 30 years.
Symptoms: Scotomas are the most common presenting compliant (90%), followed by blurred vision, photopsia, floaters, metamorphopsia and decreased peripheral vision.
Signs: The anterior segment is usually quiet. Fundus lesions are multiple grey white small round lesions, which are seen scattered throughout the posterior pole. They rarely extend to the midperiphery. The lack of vitreous inflammation is the hallmark of PIC. With time, these lesions evolve into chorioretinal scars, eventually becoming more distinct and pigmented. The occurrence of CNVM is 17–40%. Recurrence of the disease is common.
Fluorescein angiography: PIC lesion can appear hyperfluorescent in the early phase [Figure 8], or may appear as blocked fluorescence. In later phases, staining of the lesion can occur. More lesions are seen on FFA than clinically visible lesions.
|Figure 8: PIC (punctate Inner Choroiditis) lesion- hyperfluorescence in early phase|
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OCT: A homogenous thickening is seen overlying chorioretinal lesions. There is a sub-RPE solid material that pushes up the RPE and may extend up to retina.
Treatment: No treatment is required except in the case of CNV and cystoids macular edema. Systemic steroids may be considered for eyes presenting with poor visual acuity or in multiple PIC lesions in proximity to the fovea.
It is a multisystem granulomatous disorder of unknown etiology with systemic and ocular manifestations (25–50%).
Signs: Patients present with signs of anterior uveitis either acutely or as chronic granulomatous iridocyclitis. Posterior uveitis occurs in 25% of the cases. Sarcoid associated posterior uveitis has been known to be chronic and presents in the late course of the disease. It is characterized by choroidal [Figure 9]; subretinal, preretinal, macular, and optic disc granulomas. Vitreous infiltration can appear as “snow balls” or a “string of pearls.” Vessels have perivascular exudates appearing as candle wax drippings.
Macula may be involved by granuloma. Cystoid macular edema may be noted as a part of posterior uveitis or panuveitis. Large inflammatory choroidal granuloma, which can involve the macula, has been noted.
Diagnosis: Once a clinical diagnosis of sarcoid is made, the patient is subjected to a systemic review. Serological tests consist of
- Angiotensin-converting enzyme
- Serum calcium and phosphorus
- Serum lysozyme.
HRCT chest and negative Monteux test helps to clinch the diagnosis.
Treatment: Responds well to systemic steroids and immunosuppressive therapy. Systemic immunomodulatory therapy with methotrexate is very effective in sarcoid-associated posterior uveitis. There are reports of good visual recovery of choroidal granuloma with IVTA.
Posterior pole Vogt Koyanagi Harada
It is an uncommon, multisystem disease characterized by chronic, bilateral, diffuse, granulomatous, panuveitis accompanying integumentary, neurologic, and auditory involvement.
Symptoms: Commonly presents with blurring of vision in both eyes, following a prodromal stage marked by flulike symptoms.
Etiology: Is a cell-mediated autoimmune process driven by T lymphocytes directed against self-antigens associated with melanocytes in genetically suspected individuals. Diffuse choroiditis manifests either as focal area of subretinal fluid or bullous serous RD [Figure 10]. It can involve posterior pole only.
|Figure 10: Bullous serous retinal detachment in Vogt-Koyanagi-Harada syndrome|
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Investigations: FFA demonstrates multiple pinpoint hyperflourescent dots at the level of RPE which gradually enlarge and pool in the underlying area of exudative retinal detachment.
Ultrasonography shows diffuse, low-to-medium reflective thickening of posterior choroid [Figure 10].
Management: High dose of oral corticosteroids 80–100 mg or intravenous methylprednisolone pulse therapy 1 g daily for 3 consecutive days followed by high dose oral corticosteroids and slow taper are the mainstay of therapy. Cyclosporine, azathioprine, and cyclophosphamide are the preferred immunosuppressives used in the management of VKH.
Sympathetic ophthalmia involving posterior pole
It is a rare bilateral diffuse granulomatous uveitis that occurs a few days to several decades after penetrating accidental or surgical trauma to an eye. The clinical symptoms and signs are usually detected in the sympathizing eye within the first 3 months after trauma to the fellow eye.
Pathogenesis: It has been proposed that an immunological basis for sympathetic ophthalmia (SO) in which a T-cell mediated autoimmune response against an antigenic uveal protein. The inflammation does not involve the choriocapillaries or retina.
Symptoms: It varies with respect to severity and onset, ranging from minimal problems in vision, mild photophobia, pain, and slight redness to severe granulomatous panuveitis.
Signs: Posterior segment findings include moderate to severe vitritis, hyperemia, and edema of the disc, diffuse edema and exudative detachment of the retina [Figure 11] with characteristic midequatorial yellowish white choroidal lesions called dalen–fuchs nodules.
Diagnosis: The diagnosis of SO is based on history and clinical examination. There is no specific laboratory test to establish the diagnosis of SO. FFA typically demonstrates multiple hyperflourescent leakage sites that persist into the late phases.
Treatment: The main stay of therapy for SO is immunomodulatory therapy initially with systemic corticosteroids. Large doses of corticosteroids should be given early in the course of the disease and continued for at least 6 months. In patients with medical problems or systemic or ophthalmological complications related to long-term usage of systemic steroids, immunosuppressive agents are used.
Commonly used immunosuppressives in the management are azathioprine, cyclosporine and mycophenolate mofetil.
Late macula related complications are persistent CMO, epiretinal membrane formation, CNV, and subretinal fibrosis.
Summary of inflammatory macular diseases
- Treating IMD is a diagnostic and therapeutic challenge
- It needs aggressive treatment because vision maybe compromised despite aggressive treatment
- More chances of CNV.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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