Int Ophthalmol DOI 10.1007/s10792-013-9891-7
ORIGINAL PAPER
Post-fever retinitis: a single center experience from south India Srilatha Vishwanath • Kalpana Badami K. S. Sriprakash • B. L. Sujatha • S. D. Shashidhar • Y. D. Shilpa
•
Received: 25 October 2013 / Accepted: 9 December 2013 Ó Springer Science+Business Media Dordrecht 2013
Abstract Various retinal manifestations can occur following a febrile illness due to viral, bacterial or protozoal etiology. As there are limited data in the literature, we undertook this study to analyse the clinical presentation of post-fever retinitis due to various etiologies, as well as its course and management. This was a retrospective study of 14 consecutive cases who presented to the Vitreo Retina Department of our hospital over a 1-year period between January 2010 and December 2010. All patients underwent detailed ophthalmic examination and relevant investigations including fundus fluorescein angiography and optical coherence tomography (OCT). Basic and specific investigations were performed as necessary. All patients were given systemic steroids which were tapered based on clinical response. Twenty-one eyes of 14 patients (7 bilateral, 7 unilateral) were studied. Onset of ocular symptoms was approximately 3 weeks after fever. Four patients had specific etiology—one each of chikungunya, enteric fever, malaria and abdominal abscess with pneumococcal pneumonia. The presenting visual acuity of the affected eyes averaged 2/60. Six eyes had relative afferent pupillary defect. All patients had solitary or multiple patches of S. Vishwanath (&) K. Badami K. S. Sriprakash B. L. Sujatha S. D. Shashidhar Y. D. Shilpa Division of Vitreo Retina, Department of Ophthalmology, Minto Ophthalmic Hospital, Bangalore Medical College and Research Institute (BMC & RI), Bangalore, Karnataka, India e-mail: [email protected]
retinitis at the posterior pole and exudation at the macula. OCT through the lesions revealed inner retinal hyperreflectivity and thickening with after-shadowing. All patients showed improvement in vision with unilateral cases improving to an average of 6/12 and bilateral cases improving to an average of 6/24. Patients also showed resolution of retinitis, macular edema and serous detachment. Post-fever retinitis as a condition manifested approximately 3 weeks after onset of fever. Irrespective of the cause of the fever, clinical presentation of cases was similar with inner retinitis at the posterior pole and a favourable response to steroids, suggesting a possible immunological basis for this condition. Keywords Post-fever retinitis Malaria Chikungunya Typhoid India Steroids
Introduction A variety of ocular manifestations noticed after fever episodes include conjunctival congestion, uveitis, episcleritis, neuroretinitis, retinitis, and dacryoadenitis. There is an anecdotal case report of dengue fever causing panophthalmitis. These manifestations may be the result of direct invasion of the pathogen or by indirect invasion mediated through immune mechanisms. Post-fever retinitis as an entity usually manifests between 2 and
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4 weeks after the fever in the immunocompetent. Patients typically present with diminution of vision that is sudden in onset and painless. Patients can have varied posterior segment manifestations including focal and multifocal patches of retinitis, possible optic nerve involvement, serous detachment at the macula, macular edema and localized involvement of the retinal vessel. Early referral to an ophthalmologist by the treating physician would result in a better functional outcome for the patient.
Table 1 Comparison of unilateral and bilateral cases at baseline
Background and purpose
physician clearance. At each visit, BCVA, anterior and posterior segment evaluation, fundus photography, and OCT was performed. Clinical response was assessed based on BCVA, anterior and posterior segment findings (resolution of inflammation and retinitis), and OCT. The steroids were tapered over a period of 6 weeks based on the clinical response.
Various retinal manifestations can occur following a febrile illness due to viral, bacterial or protozoal etiology. As there is limited data in the literature, we undertook this retrospective study to analyse the clinical presentation of post-fever retinitis due to various etiologies as well as its course and management.
Parameters
Unilateral
Bilateral
Age (average)
31 years
33 years
Sex
5 male, 2 female
7 male
Duration between fever and onset of eye symptoms
18 days
25 days
Visual acuity at presentation
2/60
2/60
Relative afferent pupillary defect
71 %
21 %
Materials and methods
Results
This was a retrospective study of 14 consecutive patients attending the Vitreo Retina Division of the Regional Institute of Ophthalmology, South India between January 2010 and December 2010. Cases of post-fever retinitis, both unilateral and bilateral, were included and those patients with media opacity, preexisting macular or optic nerve pathology or any preexisting retinopathy were excluded. All patients underwent detailed ocular examination that included best-corrected visual acuity (BCVA), anterior and posterior segment evaluation, intraocular pressure, fundus photography, fundus fluorescein angiography, and optical coherence tomography (OCT; Stratus 3). Basic investigations included complete hemogram, erythrocyte sedimentation rate, veneral disease research laboratory tests (VDRL), human immunodeficiency virus (HIV) ELISA, Mantoux test, and chest X-ray. Other investigations were carried out as necessary, including toxoplasma immunoglobulin (Ig) G, IgM, Widal test, chikungunya IgG/IgM, dengue IgG/ IgM, malaria parasite, polymerase chain reaction for herpes simplex virus and varicella zoster virus (HSV/ HZV). All patients were given oral steroids (prednisolone) at a dose of 1 mg/kg body weight after obtaining
A total of 14 patients (7 unilateral, 7 bilateral) were reviewed. The average age in the unilateral group was 31 years (range 18–39 years) and in the bilateral group was 33 years (range 18–54 years). There were 12 males (85 %) and 2 females (15 %). A comparison of unilateral and bilateral cases at baseline together with patient characteristics are summarized in Tables 1 and 2. The clinical picture in both groups at presentation was focal or multifocal retinitis patches at the posterior pole predominantly involving the peripapillary area; this was the same in all patients regardless of the etiology (Figs. 1, 2, 3, 4). All patients had vitritis. Cases with retinitis patches adjacent to the disc showed hyperemia and edema of the disc. Segmental sheathing of the vessels adjacent to retinitis patches was seen in a few cases. Fluorescein angiography was similar in all cases with initial hypofluorescence of the retinitis patches with late hyperfluorescence, leakage and staining of the adjacent vessels (Fig. 5). OCT scans at the time of presentation through the lesion showed increased hyperreflectivity with thickening of the inner retinal layers and shadowing of the outer layers (Fig. 6). Some cases showed edema of the macula while a few showed serous detachment of the
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Int Ophthalmol Table 2 Summarizing the patient characteristics at baseline and following treatment Patient no.
Age (years/ sex)
Unilateral or bilateral
Vision at presentation (RE)
Vision at presentation (LE)
Vision at 6-week follow-up (RE)
Vision at 6-week follow-up (LE)
Diagnosis
1
40/M
B/L
2/60
1/60
6/36
6/36
NA
2
27/F
B/L
6/60
6/18
6/24
6/6
Chickungunya
3
30/M
B/L
1/60
1/60
6/60
6/60
NA
4
25/F
B/L
1/60
6/6
6/36
6/6
NA
5
18/M
B/L
6/60
5/60
6/18
6/24
Typhoid
6
38/M
B/L
4/60
3/60
6/36
6/24
NA
7
39/M
B/L
3/60
2/60
6/36
6/36
NA
8
23/M
U/L LE
6/6
3/60
6/6
6/18
Malaria
9
39/M
U/L LE
6/6
1/60
6/6
6/6
Pneumococcal pneumonia and abdominal abscess
10
60/M
U/L RE
1/60
6/18
6/36
6/18
NA
11
18/M
U/L RE
6/60
6/6
6/9
6/6
NA
12
27/M
U/L LE
6/6
6/60
6/6
6/6
NA
13 14
45/M 24/M
U/L RE U/L RE
1/60 6/36
6/9 6/6
6/24 6/12
6/9 6/6
NA NA
B/L bilateral, F female, LE left eye, M male, NA not available (investigations available for febrile illness diagnosis as performed for other patients did not yield a diagnosis), RE right eye, U/L unilateral
Fig. 1 Unilateral case at presentation. A Fundus picture showing retinitis patch with serous macular detachment. B OCT through the macula shows serous macular detachment.
C OCT through the lesion shows increased hyperreflectivity of the inner layers with after-shadowing
macula and others had an accumulation of exudates at the macula (Fig. 6). The basic investigations were unremarkable for all patients. The serum of all patients was negative for human immunodeficiency virus (HIV). In terms of etiology, one patient with bilateral disease had been diagnosed with typhoid (positive Widal test), one patient had been diagnosed with chikungunya (positive IgM antibody), one patient with unilateral disease was positive for the malaria parasite—Plasmodium falciparum, and another patient had pneumococcal pneumonia with abdominal abscess. All the other patients were either not
evaluated at the time of fever or were negative for the common pathogens (malaria/dengue/typhoid/chikungunya). Blood culture and sensitivity and sputum culture were performed where required. A female patient diagnosed with chikungunya presented 4 weeks after fever with diminution of vision in both eyes and had both anterior chamber and vitreous cells, and relative afferent pupillary defect (RAPD) in the right eye. The patient had bilateral retinitis at the posterior pole with macular edema and serous detachment. A male patient diagnosed with typhoid presented with bilateral diminution of vision
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Fig. 2 The same unilateral case as seen in Fig. 1 at 6-week follow-up. A Fundus picture showing resolution of retinitis with few hard exudates at the macula. B OCT through the macula Fig. 3 Bilateral case at presentation and follow-up. Right eye. A Fundus picture showing retinitis patch at the macula. B OCT showing inner layer hyperreflectivity with serous detachment. C Fundus picture at 6-week follow-up showing resolution of retinitis with hard exudates at the macula. D OCT at 6-week follow-up shows minimal serous detachment at the macula
Fig. 4 The same bilateral case as seen in Fig. 3 at presentation and follow-up. Left eye. A Fundus picture showing retinitis superonasal to the disc with normal macula. B Fundus picture at 6-week follow-up showing resolution of retinitis with hard exudates. C OCT at the macula appears normal. D OCT at 6-week follow-up shows normal macula
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shows minimal fluid in the subretinal space. C OCT through the lesion shows decreased hyperreflectivity and thinning of the retina
Int Ophthalmol Fig. 5 Fundus fluorescein angiography (FFA). A Fundus picture showing retinitis patch. B Early FFA showing hypofluorescence of the lesion. C AV phase of FFA showing some hyperfluorescence at the lesion. D Late-phase FFA showing hyperfluorescence at the lesion
Fig. 6 Optical coherence tomography. A OCT through the lesion in a case showing increased hyperreflectivity and thickening with aftershadowing. B OCT through the macula in the same case showing both macular edema and serous foveal detachment
6 weeks later. He had bilateral vitritis with retinitis at the posterior pole with localized vasculitis and macular edema. A male patient diagnosed with malaria presented 2 weeks later with diminution of vision in the left eye. He had vitritis, RAPD, retinitis with many hemorrhages with localized vasculitis and macular edema. A male patient with bilateral sputum-proven pneumococcal pneumonia and abdominal abscess presented after 1 week with sudden diminution of vision in the left eye. He had vitritis and RAPD with a solitary patch of retinitis in the posterior pole. Tests for HIV, toxoplasma, HSV, and HZV proved negative. These patients with specific etiology also had a favorable response to steroids similar to those without a specific diagnosis.
With steroid therapy (oral prednisolone) at a dosage of 1 mg/kg body weight tapered over a period of 6 weeks based on clinical response, all patients showed a gradual resolution of retinitis irrespective of etiology and also resolution of macular edema and serous detachment. We also observed that the number of exudates increased with the resolution of macular edema. All patients had a gain in visual acuity. The patients with unilateral disease had an average visual acuity of 6/12 at 6 weeks followup while those with bilateral disease had an average visual acuity of 6/24. Patients with exudative plaques at the fovea had a smaller gain in visual acuity. Follow-up OCT scans showed a decrease in hyperreflectivity and optical shadowing with thinning of retinal layers. There was resolution of macular edema and serous detachment.
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Discussion Post-fever retinitis usually manifests approximately 3 weeks after the onset of fever irrespective of etiology. The usual manifestations include focal or multifocal patches of retinitis which could be unilateral or bilateral and may be associated with RAPD, anterior uveitis, macular edema, and serous detachment at the macula. All patients in the current study showed a good response to oral steroids. A literature search showed this study to be the largest series of post-fever retinitis from a single center. Viral retinitis can present with focal or multifocal retinitis and follows acute viral systemic illness. This is apart from the typical manifestations of cytomegalovirus, HSV, and HZV [1, 2]. In our case series, 10 out of 14 patients did not have an etiological diagnosis for the fever and most probably had an acute viral systemic illness after which they presented with focal or multifocal retinitis. Chikungunya virus infection could have various ocular manifestations as reported in case reports and case series. One case series reported granulomatous and non-granulomatous uveitis, optic neuritis, and dendritic lesions as common lesions with good visual prognosis [3]. In a case report, Mahesh et al. [4] reported a patient who presented with bilateral neuroretinitis associated with chikungunya infection. A more recent case series found iridocyclitis and retinitis to be the most common ocular manifestation with episcleritis seen more rarely [5]. Murthy et al. [6] observed that a serologically proven chikungunya patient with bilateral retinitis did not respond to systemic acyclovir or steroids but had a self-limiting course. One of our patients who was positive for IgM chikungunya had bilateral anterior non-granulomatous uveitis and retinitis with optic nerve involvement in one eye who showed a favourable response to oral steroids. Malaria retinopathy which includes patchy retinal whitening and focal changes in vessel color is thought to be a defining characteristic of cerebral malaria due to Plasmodium falciparum. This condition is usually bilateral and may be associated with papilloedema and white-centered hemorrhages [7]. Our patient, who was positive for malaria parasite, had a unilateral large retinitis patch with vascular sheathing and RAPD. He had no evidence of cerebral malaria. Anterior and posterior uveitis, scleritis, and glaucoma have all been described as possible sequelae of
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post-streptococcal infection [8–10]. One of our patients who had an abdominal abscess and pneumonia presented with bilateral anterior uveitis and vitritis with a left eye showing solitary patch of retinitis and RAPD. In a case report of a patient with typhoid fever, bilateral chorioretinitis with stellate maculopathy was found in one eye [11]. Our series included a patient who was treated for enteric fever 6 weeks prior to the onset of ocular symptoms. He presented with bilateral anterior uveitis, vitritis, multifocal patches of retinitis, macular edema and localized retinal vascular sheathing. In a case series, fundus fluorescein angiography of retinitis was seen as early hypofluorescence with late hyperfluorescence with disc leakage [5]. This was similar to the findings in our series where all patients showed early hypofluorescence and late hyeprfluorescence of the retinitis patches, disc leakage, and localized staining of vessels in some cases. In the same series, OCT showed hyperreflectivity of the nerve fiber layer with after-shadowing in the areas of retinitis associated with fluid-filled spaces in the outer retina and subfoveal serous detachment [5]. In our patients we also had similar findings with hyperreflectivity in the inner layers with after-shadowing corresponding to areas of retinitis. Some patients had associated macular edema and/or subfoveal detachment. On follow-up, the hyperreflectivity decreased in the areas of retinitis and the areas showed evidence of atrophy. Several studies have shown that the presentation of this condition several days to weeks after a systemic illness suggests an immunological basis for this condition. An immunological basis was shown in another case series of dengue maculopathy where they demonstrated a decrease in C3 complement levels [12]. A similar presentation was seen in our study with patients presenting an average of 3 weeks after the onset of fever and having a uniform good response to steroids irrespective of etiology, indicating a possible immunological role in this condition. Some case reports and case series have managed the patients conservatively as they believe it to be a selflimiting condition. In one case report, a patient with bilateral neuroretinitis following chikungunya fever was treated with both systemic antiviral medication and steroids (prednisolone) at 1 mg/kg but did not find any major benefit [4]. Another case series of patients with retinitis following chikunugunya fever were
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treated with systemic acyclovir and steroids at 1 mg/kg body weight and were found to have significant visual benefit [5]. In our series, all patients were treated with oral prednisolone at 1 mg/kg body weight irrespective of etiology and the steroids were tapered based on clinical response over a period of 6 weeks. All our patients irrespective of etiology had improvement in vision with unilateral cases improving from 2/60 vision to 6/12 and bilateral cases improving from an average 2/60 vision to 6/24. We also found that patients who had hard exudates or plaques at the fovea had least improvement in vision.
Conclusions Post-fever retinitis as a condition manifested approximately 3 weeks after onset of fever. Irrespective of the cause of fever in these patients, the clinical presentation was similar with inner retinitis at the posterior pole with or without optic nerve involvement. The presentation 3 weeks after systemic infection suggests a possible immunological basis for this condition. All patients also had a favorable response to oral steroids irrespective of their prior systemic infection. This study highlights the need for a high index of suspicion by an ophthalmologist to diagnose this entity and for the early institution of steroids for rapid improvement in symptoms and prevention of visual loss.
References 1. Yoser SL, Forster DJ, Rao NA (1993) Systemic viral infections and their retinal and choroidal manifestations. Surv Ophthalmol 37(3):13–352 2. Khairallah M, Jelliti B, Jenzeri S (2009) Emergent infectious uveitis. Middle East Afr J Ophthalmol 16(4):225–238 3. Lalitha P, Rathinam S, Banushree K, Maheshkumar S, Vijayakumar R, Sathe P (2007) Ocular involvement associated with an epidemic outbreak of chikungunya virus infection. Am J Ophthalmol 144(4):552–556 4. Mahesh G, Giridhar A, Shedbele A, Kumar R, Saikumar SJ (2009) A case of bilateral presumed chikungunya neuroretinitis. Indian J Ophthalmol 57(2):148–150 5. Mahendradas P, Ranganna SK, Shetty R, Balu R, Narayana KM, Babu RB, Shetty BK (2008) Ocular manifestations associated with chikungunya. Ophthalmology 115(2):287–291 6. Murthy KR, Venkataraman N, Satish V, Babu K (2008) Bilateral retinitis following Chikungunya fever. Indian J Ophthalmol 56(4):329–331 7. Beare NA, Lewallen S, Taylor TE, Molyneux ME (2011) Redefining cerebral malaria by including malaria retinopathy. Future Microbiol 6(3):349–355 8. Leiba H, Barash J, Pollack AL (1998) Poststreptococcal uveitis. Am J Ophthalmol 126:317–318 9. Ortiz JM, Kamerling JM, Fisher D, Baxter J (1995) Scleritis, uveitis, and glaucoma in a patient with rheumatic fever. Am J Ophthalmol 120:538–539 10. Besada E, Frauens BJ, Schatz S (2004) Choroiditis, pigment epithelial detachment, and cystoid macular edema as complications of poststreptococcal syndrome. Optom Vis Sci 81:578–585 11. Fusco R, Magli A, Guacci P (1986) Stellate maculopathy due to Salmonella typhi. A case report. Ophthalmologica 192(3):154–158 12. Hsien-Wen SuD, Bacsal K, Chee S-P et al (2007) Prevalence of dengue maculopathy in patients hospitalized for dengue fever. Ophthalmology 114:1743–1747
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ORIGINAL PAPER
Post-fever retinitis: a single center experience from south India Srilatha Vishwanath • Kalpana Badami K. S. Sriprakash • B. L. Sujatha • S. D. Shashidhar • Y. D. Shilpa
•
Received: 25 October 2013 / Accepted: 9 December 2013 Ó Springer Science+Business Media Dordrecht 2013
Abstract Various retinal manifestations can occur following a febrile illness due to viral, bacterial or protozoal etiology. As there are limited data in the literature, we undertook this study to analyse the clinical presentation of post-fever retinitis due to various etiologies, as well as its course and management. This was a retrospective study of 14 consecutive cases who presented to the Vitreo Retina Department of our hospital over a 1-year period between January 2010 and December 2010. All patients underwent detailed ophthalmic examination and relevant investigations including fundus fluorescein angiography and optical coherence tomography (OCT). Basic and specific investigations were performed as necessary. All patients were given systemic steroids which were tapered based on clinical response. Twenty-one eyes of 14 patients (7 bilateral, 7 unilateral) were studied. Onset of ocular symptoms was approximately 3 weeks after fever. Four patients had specific etiology—one each of chikungunya, enteric fever, malaria and abdominal abscess with pneumococcal pneumonia. The presenting visual acuity of the affected eyes averaged 2/60. Six eyes had relative afferent pupillary defect. All patients had solitary or multiple patches of S. Vishwanath (&) K. Badami K. S. Sriprakash B. L. Sujatha S. D. Shashidhar Y. D. Shilpa Division of Vitreo Retina, Department of Ophthalmology, Minto Ophthalmic Hospital, Bangalore Medical College and Research Institute (BMC & RI), Bangalore, Karnataka, India e-mail: [email protected]
retinitis at the posterior pole and exudation at the macula. OCT through the lesions revealed inner retinal hyperreflectivity and thickening with after-shadowing. All patients showed improvement in vision with unilateral cases improving to an average of 6/12 and bilateral cases improving to an average of 6/24. Patients also showed resolution of retinitis, macular edema and serous detachment. Post-fever retinitis as a condition manifested approximately 3 weeks after onset of fever. Irrespective of the cause of the fever, clinical presentation of cases was similar with inner retinitis at the posterior pole and a favourable response to steroids, suggesting a possible immunological basis for this condition. Keywords Post-fever retinitis Malaria Chikungunya Typhoid India Steroids
Introduction A variety of ocular manifestations noticed after fever episodes include conjunctival congestion, uveitis, episcleritis, neuroretinitis, retinitis, and dacryoadenitis. There is an anecdotal case report of dengue fever causing panophthalmitis. These manifestations may be the result of direct invasion of the pathogen or by indirect invasion mediated through immune mechanisms. Post-fever retinitis as an entity usually manifests between 2 and
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4 weeks after the fever in the immunocompetent. Patients typically present with diminution of vision that is sudden in onset and painless. Patients can have varied posterior segment manifestations including focal and multifocal patches of retinitis, possible optic nerve involvement, serous detachment at the macula, macular edema and localized involvement of the retinal vessel. Early referral to an ophthalmologist by the treating physician would result in a better functional outcome for the patient.
Table 1 Comparison of unilateral and bilateral cases at baseline
Background and purpose
physician clearance. At each visit, BCVA, anterior and posterior segment evaluation, fundus photography, and OCT was performed. Clinical response was assessed based on BCVA, anterior and posterior segment findings (resolution of inflammation and retinitis), and OCT. The steroids were tapered over a period of 6 weeks based on the clinical response.
Various retinal manifestations can occur following a febrile illness due to viral, bacterial or protozoal etiology. As there is limited data in the literature, we undertook this retrospective study to analyse the clinical presentation of post-fever retinitis due to various etiologies as well as its course and management.
Parameters
Unilateral
Bilateral
Age (average)
31 years
33 years
Sex
5 male, 2 female
7 male
Duration between fever and onset of eye symptoms
18 days
25 days
Visual acuity at presentation
2/60
2/60
Relative afferent pupillary defect
71 %
21 %
Materials and methods
Results
This was a retrospective study of 14 consecutive patients attending the Vitreo Retina Division of the Regional Institute of Ophthalmology, South India between January 2010 and December 2010. Cases of post-fever retinitis, both unilateral and bilateral, were included and those patients with media opacity, preexisting macular or optic nerve pathology or any preexisting retinopathy were excluded. All patients underwent detailed ocular examination that included best-corrected visual acuity (BCVA), anterior and posterior segment evaluation, intraocular pressure, fundus photography, fundus fluorescein angiography, and optical coherence tomography (OCT; Stratus 3). Basic investigations included complete hemogram, erythrocyte sedimentation rate, veneral disease research laboratory tests (VDRL), human immunodeficiency virus (HIV) ELISA, Mantoux test, and chest X-ray. Other investigations were carried out as necessary, including toxoplasma immunoglobulin (Ig) G, IgM, Widal test, chikungunya IgG/IgM, dengue IgG/ IgM, malaria parasite, polymerase chain reaction for herpes simplex virus and varicella zoster virus (HSV/ HZV). All patients were given oral steroids (prednisolone) at a dose of 1 mg/kg body weight after obtaining
A total of 14 patients (7 unilateral, 7 bilateral) were reviewed. The average age in the unilateral group was 31 years (range 18–39 years) and in the bilateral group was 33 years (range 18–54 years). There were 12 males (85 %) and 2 females (15 %). A comparison of unilateral and bilateral cases at baseline together with patient characteristics are summarized in Tables 1 and 2. The clinical picture in both groups at presentation was focal or multifocal retinitis patches at the posterior pole predominantly involving the peripapillary area; this was the same in all patients regardless of the etiology (Figs. 1, 2, 3, 4). All patients had vitritis. Cases with retinitis patches adjacent to the disc showed hyperemia and edema of the disc. Segmental sheathing of the vessels adjacent to retinitis patches was seen in a few cases. Fluorescein angiography was similar in all cases with initial hypofluorescence of the retinitis patches with late hyperfluorescence, leakage and staining of the adjacent vessels (Fig. 5). OCT scans at the time of presentation through the lesion showed increased hyperreflectivity with thickening of the inner retinal layers and shadowing of the outer layers (Fig. 6). Some cases showed edema of the macula while a few showed serous detachment of the
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Int Ophthalmol Table 2 Summarizing the patient characteristics at baseline and following treatment Patient no.
Age (years/ sex)
Unilateral or bilateral
Vision at presentation (RE)
Vision at presentation (LE)
Vision at 6-week follow-up (RE)
Vision at 6-week follow-up (LE)
Diagnosis
1
40/M
B/L
2/60
1/60
6/36
6/36
NA
2
27/F
B/L
6/60
6/18
6/24
6/6
Chickungunya
3
30/M
B/L
1/60
1/60
6/60
6/60
NA
4
25/F
B/L
1/60
6/6
6/36
6/6
NA
5
18/M
B/L
6/60
5/60
6/18
6/24
Typhoid
6
38/M
B/L
4/60
3/60
6/36
6/24
NA
7
39/M
B/L
3/60
2/60
6/36
6/36
NA
8
23/M
U/L LE
6/6
3/60
6/6
6/18
Malaria
9
39/M
U/L LE
6/6
1/60
6/6
6/6
Pneumococcal pneumonia and abdominal abscess
10
60/M
U/L RE
1/60
6/18
6/36
6/18
NA
11
18/M
U/L RE
6/60
6/6
6/9
6/6
NA
12
27/M
U/L LE
6/6
6/60
6/6
6/6
NA
13 14
45/M 24/M
U/L RE U/L RE
1/60 6/36
6/9 6/6
6/24 6/12
6/9 6/6
NA NA
B/L bilateral, F female, LE left eye, M male, NA not available (investigations available for febrile illness diagnosis as performed for other patients did not yield a diagnosis), RE right eye, U/L unilateral
Fig. 1 Unilateral case at presentation. A Fundus picture showing retinitis patch with serous macular detachment. B OCT through the macula shows serous macular detachment.
C OCT through the lesion shows increased hyperreflectivity of the inner layers with after-shadowing
macula and others had an accumulation of exudates at the macula (Fig. 6). The basic investigations were unremarkable for all patients. The serum of all patients was negative for human immunodeficiency virus (HIV). In terms of etiology, one patient with bilateral disease had been diagnosed with typhoid (positive Widal test), one patient had been diagnosed with chikungunya (positive IgM antibody), one patient with unilateral disease was positive for the malaria parasite—Plasmodium falciparum, and another patient had pneumococcal pneumonia with abdominal abscess. All the other patients were either not
evaluated at the time of fever or were negative for the common pathogens (malaria/dengue/typhoid/chikungunya). Blood culture and sensitivity and sputum culture were performed where required. A female patient diagnosed with chikungunya presented 4 weeks after fever with diminution of vision in both eyes and had both anterior chamber and vitreous cells, and relative afferent pupillary defect (RAPD) in the right eye. The patient had bilateral retinitis at the posterior pole with macular edema and serous detachment. A male patient diagnosed with typhoid presented with bilateral diminution of vision
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Fig. 2 The same unilateral case as seen in Fig. 1 at 6-week follow-up. A Fundus picture showing resolution of retinitis with few hard exudates at the macula. B OCT through the macula Fig. 3 Bilateral case at presentation and follow-up. Right eye. A Fundus picture showing retinitis patch at the macula. B OCT showing inner layer hyperreflectivity with serous detachment. C Fundus picture at 6-week follow-up showing resolution of retinitis with hard exudates at the macula. D OCT at 6-week follow-up shows minimal serous detachment at the macula
Fig. 4 The same bilateral case as seen in Fig. 3 at presentation and follow-up. Left eye. A Fundus picture showing retinitis superonasal to the disc with normal macula. B Fundus picture at 6-week follow-up showing resolution of retinitis with hard exudates. C OCT at the macula appears normal. D OCT at 6-week follow-up shows normal macula
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shows minimal fluid in the subretinal space. C OCT through the lesion shows decreased hyperreflectivity and thinning of the retina
Int Ophthalmol Fig. 5 Fundus fluorescein angiography (FFA). A Fundus picture showing retinitis patch. B Early FFA showing hypofluorescence of the lesion. C AV phase of FFA showing some hyperfluorescence at the lesion. D Late-phase FFA showing hyperfluorescence at the lesion
Fig. 6 Optical coherence tomography. A OCT through the lesion in a case showing increased hyperreflectivity and thickening with aftershadowing. B OCT through the macula in the same case showing both macular edema and serous foveal detachment
6 weeks later. He had bilateral vitritis with retinitis at the posterior pole with localized vasculitis and macular edema. A male patient diagnosed with malaria presented 2 weeks later with diminution of vision in the left eye. He had vitritis, RAPD, retinitis with many hemorrhages with localized vasculitis and macular edema. A male patient with bilateral sputum-proven pneumococcal pneumonia and abdominal abscess presented after 1 week with sudden diminution of vision in the left eye. He had vitritis and RAPD with a solitary patch of retinitis in the posterior pole. Tests for HIV, toxoplasma, HSV, and HZV proved negative. These patients with specific etiology also had a favorable response to steroids similar to those without a specific diagnosis.
With steroid therapy (oral prednisolone) at a dosage of 1 mg/kg body weight tapered over a period of 6 weeks based on clinical response, all patients showed a gradual resolution of retinitis irrespective of etiology and also resolution of macular edema and serous detachment. We also observed that the number of exudates increased with the resolution of macular edema. All patients had a gain in visual acuity. The patients with unilateral disease had an average visual acuity of 6/12 at 6 weeks followup while those with bilateral disease had an average visual acuity of 6/24. Patients with exudative plaques at the fovea had a smaller gain in visual acuity. Follow-up OCT scans showed a decrease in hyperreflectivity and optical shadowing with thinning of retinal layers. There was resolution of macular edema and serous detachment.
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Discussion Post-fever retinitis usually manifests approximately 3 weeks after the onset of fever irrespective of etiology. The usual manifestations include focal or multifocal patches of retinitis which could be unilateral or bilateral and may be associated with RAPD, anterior uveitis, macular edema, and serous detachment at the macula. All patients in the current study showed a good response to oral steroids. A literature search showed this study to be the largest series of post-fever retinitis from a single center. Viral retinitis can present with focal or multifocal retinitis and follows acute viral systemic illness. This is apart from the typical manifestations of cytomegalovirus, HSV, and HZV [1, 2]. In our case series, 10 out of 14 patients did not have an etiological diagnosis for the fever and most probably had an acute viral systemic illness after which they presented with focal or multifocal retinitis. Chikungunya virus infection could have various ocular manifestations as reported in case reports and case series. One case series reported granulomatous and non-granulomatous uveitis, optic neuritis, and dendritic lesions as common lesions with good visual prognosis [3]. In a case report, Mahesh et al. [4] reported a patient who presented with bilateral neuroretinitis associated with chikungunya infection. A more recent case series found iridocyclitis and retinitis to be the most common ocular manifestation with episcleritis seen more rarely [5]. Murthy et al. [6] observed that a serologically proven chikungunya patient with bilateral retinitis did not respond to systemic acyclovir or steroids but had a self-limiting course. One of our patients who was positive for IgM chikungunya had bilateral anterior non-granulomatous uveitis and retinitis with optic nerve involvement in one eye who showed a favourable response to oral steroids. Malaria retinopathy which includes patchy retinal whitening and focal changes in vessel color is thought to be a defining characteristic of cerebral malaria due to Plasmodium falciparum. This condition is usually bilateral and may be associated with papilloedema and white-centered hemorrhages [7]. Our patient, who was positive for malaria parasite, had a unilateral large retinitis patch with vascular sheathing and RAPD. He had no evidence of cerebral malaria. Anterior and posterior uveitis, scleritis, and glaucoma have all been described as possible sequelae of
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post-streptococcal infection [8–10]. One of our patients who had an abdominal abscess and pneumonia presented with bilateral anterior uveitis and vitritis with a left eye showing solitary patch of retinitis and RAPD. In a case report of a patient with typhoid fever, bilateral chorioretinitis with stellate maculopathy was found in one eye [11]. Our series included a patient who was treated for enteric fever 6 weeks prior to the onset of ocular symptoms. He presented with bilateral anterior uveitis, vitritis, multifocal patches of retinitis, macular edema and localized retinal vascular sheathing. In a case series, fundus fluorescein angiography of retinitis was seen as early hypofluorescence with late hyperfluorescence with disc leakage [5]. This was similar to the findings in our series where all patients showed early hypofluorescence and late hyeprfluorescence of the retinitis patches, disc leakage, and localized staining of vessels in some cases. In the same series, OCT showed hyperreflectivity of the nerve fiber layer with after-shadowing in the areas of retinitis associated with fluid-filled spaces in the outer retina and subfoveal serous detachment [5]. In our patients we also had similar findings with hyperreflectivity in the inner layers with after-shadowing corresponding to areas of retinitis. Some patients had associated macular edema and/or subfoveal detachment. On follow-up, the hyperreflectivity decreased in the areas of retinitis and the areas showed evidence of atrophy. Several studies have shown that the presentation of this condition several days to weeks after a systemic illness suggests an immunological basis for this condition. An immunological basis was shown in another case series of dengue maculopathy where they demonstrated a decrease in C3 complement levels [12]. A similar presentation was seen in our study with patients presenting an average of 3 weeks after the onset of fever and having a uniform good response to steroids irrespective of etiology, indicating a possible immunological role in this condition. Some case reports and case series have managed the patients conservatively as they believe it to be a selflimiting condition. In one case report, a patient with bilateral neuroretinitis following chikungunya fever was treated with both systemic antiviral medication and steroids (prednisolone) at 1 mg/kg but did not find any major benefit [4]. Another case series of patients with retinitis following chikunugunya fever were
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treated with systemic acyclovir and steroids at 1 mg/kg body weight and were found to have significant visual benefit [5]. In our series, all patients were treated with oral prednisolone at 1 mg/kg body weight irrespective of etiology and the steroids were tapered based on clinical response over a period of 6 weeks. All our patients irrespective of etiology had improvement in vision with unilateral cases improving from 2/60 vision to 6/12 and bilateral cases improving from an average 2/60 vision to 6/24. We also found that patients who had hard exudates or plaques at the fovea had least improvement in vision.
Conclusions Post-fever retinitis as a condition manifested approximately 3 weeks after onset of fever. Irrespective of the cause of fever in these patients, the clinical presentation was similar with inner retinitis at the posterior pole with or without optic nerve involvement. The presentation 3 weeks after systemic infection suggests a possible immunological basis for this condition. All patients also had a favorable response to oral steroids irrespective of their prior systemic infection. This study highlights the need for a high index of suspicion by an ophthalmologist to diagnose this entity and for the early institution of steroids for rapid improvement in symptoms and prevention of visual loss.
References 1. Yoser SL, Forster DJ, Rao NA (1993) Systemic viral infections and their retinal and choroidal manifestations. Surv Ophthalmol 37(3):13–352 2. Khairallah M, Jelliti B, Jenzeri S (2009) Emergent infectious uveitis. Middle East Afr J Ophthalmol 16(4):225–238 3. Lalitha P, Rathinam S, Banushree K, Maheshkumar S, Vijayakumar R, Sathe P (2007) Ocular involvement associated with an epidemic outbreak of chikungunya virus infection. Am J Ophthalmol 144(4):552–556 4. Mahesh G, Giridhar A, Shedbele A, Kumar R, Saikumar SJ (2009) A case of bilateral presumed chikungunya neuroretinitis. Indian J Ophthalmol 57(2):148–150 5. Mahendradas P, Ranganna SK, Shetty R, Balu R, Narayana KM, Babu RB, Shetty BK (2008) Ocular manifestations associated with chikungunya. Ophthalmology 115(2):287–291 6. Murthy KR, Venkataraman N, Satish V, Babu K (2008) Bilateral retinitis following Chikungunya fever. Indian J Ophthalmol 56(4):329–331 7. Beare NA, Lewallen S, Taylor TE, Molyneux ME (2011) Redefining cerebral malaria by including malaria retinopathy. Future Microbiol 6(3):349–355 8. Leiba H, Barash J, Pollack AL (1998) Poststreptococcal uveitis. Am J Ophthalmol 126:317–318 9. Ortiz JM, Kamerling JM, Fisher D, Baxter J (1995) Scleritis, uveitis, and glaucoma in a patient with rheumatic fever. Am J Ophthalmol 120:538–539 10. Besada E, Frauens BJ, Schatz S (2004) Choroiditis, pigment epithelial detachment, and cystoid macular edema as complications of poststreptococcal syndrome. Optom Vis Sci 81:578–585 11. Fusco R, Magli A, Guacci P (1986) Stellate maculopathy due to Salmonella typhi. A case report. Ophthalmologica 192(3):154–158 12. Hsien-Wen SuD, Bacsal K, Chee S-P et al (2007) Prevalence of dengue maculopathy in patients hospitalized for dengue fever. Ophthalmology 114:1743–1747
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