Ординатура / Офтальмология / Учебные материалы / Uveitis Text and Imaging Text and Imaging Text and Imaging 2009

The ATT is given in combination with oral corticosteroids (0.8-1.0 mg/kg/day), which are gradually tapered over 3-4 months. The response to treatment is usually evident within 4 to 6 weeks. The lesions heal with outer retinal atrophy associated with minimal retinal pigmentation. The scars show central healed areas, surrounded by a border that is the last to heal.3,13 The major issue, however, is the paradoxical initial worsening of lesions seen after the initiation of ATT

in nearly 30% of the eyes which usually responds to a hike in oral corticosteroids (Figure 14).3 The recurrences are rare once the treatment is completed and, if occurs, is usually treated on the lines of multi drug resistant tuberculosis.

PROGNOSIS

The prognosis is favorable with resolution of choroidal lesions and visual improvement in nearly all the

patients. Gupta et al13 reported a final visual acuity of 20/30 or better in nearly 50% of the eyes with recurrence observed only in one of the seven patients treated. We have observed that those patients who are treated with ATT early in the course of the disease remain recurrence free and eventually have subtle scarring with minimal RPE disturbances (Figure 16). Compared to this are those patients who do not receive ATT. They continue to suffer multiple recurrences and eventually end up having extensive scarring and RPE clumping (Figure 17). Another complication observed is the development of choroidal neovascular membrane (Figure 18).

KEY POINTS

•Presumed tubercular serpiginouslike choroiditis probably represents an immune-mediated hypersensitivity reaction to the presence of a few acid-fast bacteria in the choroid or retinal pigment epithelium.

•Clinical presentations include: (1) multifocal progressive choroiditis initially presenting as few discrete areas of choroiditis that show a wavelike progression to confluent, diffuse choroiditis eventually resembling serpiginous choroiditis; (2) diffuse choroiditis presenting as confluent, plaque like choroiditis with amoeboid pattern suggestive of serpiginous choroiditis at initial presentation; and (3) a mixed variety in which the opposite eyes have different features.

•The differentiating points from the classic serpiginous choroiditis includes younger age at presentation, greater incidence of unilaterality with significant anterior segment and vitreal inflammation, additional presence of a few discrete perivascular choroiditis patches and choroidal granulomas alongside the serpiginouslike lesions in these eyes.

•These patients have systemic evidence of active or latent tuberculosis and show repeated recurrences when treated alone with corticosteroid therapy.

•The diagnosis is based on the classic clinical picture in addition to a positive Mantoux test, a chest radiograph suggestive of tuberculosis or a positive polymerase

chain reaction (PCR) result from aqueous or vitreous humor for Mycobacterium tuberculosis.

•The treatment regimen consists of prolonged course of 4-drug ATT in addition to oral corticosteroids.

•The prognosis is favorable with significant visual recovery in nearly all the eyes with only occasional episodes of recurrences.

REFERENCES

1.Bodaghi B, LeHoang P. Ocular tuberculosis [review]. Curr Opinion Ophthalmol 2000;11:443–8.

2.Helm CJ, Holland GN. Ocular tuberculosis [review]. Surv Ophthalmol 1993;38:229-56.

3.Gupta V, Gupta A, Rao NA. Intraocular Tuberculosis—An Update. Survey of Ophthalmology 2007;52:561-87.

4.Gupta A, Gupta V. Tubercular posterior uveitis. Int Ophthalmol Clin 2005;45:71-88.

5.Gupta A, Gupta V, Arora S, et al. PCR-positive tubercular retinal vasculitis: clinical characteristics and management, Retina 2001;21:435-44.

6.Gass JD. Inflammatory disease of the retina and choroid. In: Stereoscopic Atlas of Macular Disease: Diagnosis and Treatment, 4th ed. St. Louis, Mo: CV Mosby Co.; 1997;15865.

7.Weiss H, Annesley WH Jr, Shields JA, et al. The clinical course of serpiginous choroidopathy. Am J Ophthalmol 1979;87:133-42.

8.Gupta V, Agarwal A, Gupta A, et al. Clinical characteristics of serpiginous choroidopathy in North India. Am J Ophthalmol 2002;134:47-56.

9.Edelsten C, Stanford MR, Graham EM. Serpiginous choroiditis: an unusual presentation of ocular sarcoidosis. Br J Ophthalmol 1994;78:70-1.

10.Rattray KM, Cole MD, Smith SR. Systemic non-Hodgkin’s lymphoma presenting as a serpiginous choroidopathy: report of a case and review of the literature [review]. Eye 2000;14:706-10.

11.Laatikainen L, Erkkila H. Serpiginous choroiditis. Br J Ophthalmol 1974;58:777-83.

12.Priya K, Madhavan HN, Reiser BJ, Biswas J, Saptagirish R, Narayana KM, et al Association of herpesviruses in the aqueous humor of patients with serpiginous choroiditis: a polymerase chain reaction-based study. Ocul Immunol Inflamm. 2002;10:253-61.

13.Gupta V, Gupta A, Arora S, et al., Presumed tubercular serpiginouslike choroiditis: clinical presentations and management, Ophthalmology 2003;110:1744-9.

14.Rao NA, Saraswati S, Smith RE. Tuberculous uveitis: distribution of Mycobacterium tuberculosis in the retinal pigment epithelium. Arch Ophthalmol 2006;124:1777-9.

INTRODUCTION

The accumulated evidence especially through indocyanine green angiography (ICGA)1-3 now clearly indicates that primary inflammation at the level of the choriocapillaris is a common denominator for several diseases of the fundus formerly classified in the vague category of “white dot syndromes”. The ICGA pattern correlated with functional (visual field testing) and electrophysiologic parameters strongly points towards choriocapillaropathy and secondary ischaemic dysfunction of the outer retina in the group of diseases including multiple evanescent white dot syndrome (MEWDS), acute posterior multifocal placoid pigment epitheliopathy or acute multifocal ischaemic choroiditis (APMPPE/AMIC), multifocal choroiditis/ punctate inner choroidopathy (MFC/PIC) and serpiginous choroiditis.4,5

Beside these relatively well known, well defined and more commonly occurring entities, more rare entities such as acute macular neuroretinopathy (AMN) and possibly acute zonal occult outer retinopathy (AZOOR) and other described cases are probably also part of this spectrum. The rarity of the latter conditions however have not generated enough clinical data to be sure of a common mechanism.

Furthermore between these rather well determined clinical entities, intermediary forms clearly characterized by choriocapillaropathy occur that can hardly be made to fit into these categories.Thus, an intermediary form of disease between APMPPE and serpiginous choroiditis has been reported and given the name of AMPPiginous choroiditis and many more entities are being described and will be described.6 Lately another new name has been given to a similar disease pattern having the lesional aspect of APMPPE combined with the evolutionary pattern of serpiginous choroiditis with recrudescences and progression which the authors called relentless placoid chorioretinitis. The authors asked themselves whether it was a new entity or a variant of serpiginous choroiditis.7 This question

is of limited relevance as far as the mechanism, inflammatory choriocapillaropathy, is understood. More importantly the proportionally frequent occurrence of overlapping forms and intermediary forms which cannot be classified into known entities has to be taken into account. It is not absolutely essential to generate new names for such cases unless there are sufficient new consistent elements to do so. What is important is to determine whether these cases fall into the group of inflammatory choriocapillaropathies and, if this is the case, follow them appropriately by ICGA and functional tests and introduce cortisteroid ± immunosuppressants in case of unfavourable evolution.

RARE ENTITIES

ACUTE ZONAL OCCULT OUTER RETINOPATHY (AZOOR) AND ACUTE ANNULAR OUTER RETINOPATHY (AAOR) (SEE CHAPTER 22H)

Gass described in 1993 a syndrome characterised by photopsias, acute bilateral loss of outer retinal function, minimal initial fundus changes and anabnormal ERG, which he called acute zonal occult outer retinopathy (AZOOR) This entity is sharing clinical similarities with MEWDS, acute idiopathic blind spot enlargement, punctate inner choroidopathy, multifocal choroiditis with panuveitis and acute macular neuroretinopathy.8 All these conditions predominantly affect young myopic women complaining of photopsias with scotomata and ERG abnormalities which led Gass to speculate that they could be variants of the same pathology.9,10 The disease is described in details in the next chapter.

Acute annular outer retinopathy (AAOR) was first described by Luckie and colleagues and is characterised by visual field loss corresponding to a ring of white-gray discoloration of the retina evolving towards chorioretinal thinning11 and should probably be classified with AZOOR in the acute zonal outer retinopathies.12

ACUTE MACULAR NEURORETINOPATHY (AMN)

Acute macular neuroretinopathy (AMN) is a rare chorioretinopathy affecting young adults mono or bilaterally, producing disturbing symptoms of photopsias and often occuring after a flu-like illness like many of the other PICCPs.13 Visual loss is variable and fundus changes are characterised by large macular orange-brown plaques. Fluorescein angiography shows early choroidal hypofluorescence or can be unremarkable. The visual field can show a central scotoma. The photopsias, clinical signs and functional tests usually recover without sequels within weeks or months. AMN has been described in association with MEWDS in the same patient linking the disease to the other PICCPs.14 The whole picture of this entity perfectly corresponds to and is characteristic of a PICCP, but the rarity of its occurrence did not allow to have sufficient ICGA data so far. We recently saw a patient showing the typical fundus color changes associated with ICGA hypofluorescence of the whole macular area indicating choriocapillaris pathology and linking the disease to the PICCPs. ICGA showed hypofluorescence consistent with a choriocapillaropathy (Figure 1). A French group on the other hand reported a case AMN without ICGA findings.15

Figure 1: Indocyanine green angiography showing a plaque of hypofluorescence compatible with choriocapillaris hypoperfusion in a case of acute macular neuroretinopathy (AMN) (Courtesy Dr. Alessandro Mantovani, Como, Italy)

OVERLAPING CLINICAL PICTURES IN PICCP: THE CHORIOCAPILLARIS AS THE COMMON DENOMINATOR OF UNDEFINED PICCPS

ASSOCIATION OF DIFFERENT

PICCPS IN THE SAME PATIENT

Several articles have reported clinical cases combining two or more of the PICCP entities described. Holz and colleagues described acute zonal occult outer retinopathy (AZOOR) associated with multifocal choroiditis.16 Association of MEWDS and multifocal choroiditis in the same patient has been described in several reports and evolution from MEWDS to MFC as well as the reverse have been reported.17-19 Association in the same patient of acute macular neuroretinopathy and MEWDS has been described by Gass who suggested that AMN was part of the MEWDS/AIBSE spectrum.14 These and more reports represent a considerable body of evidence sugesting a common denominator for all the PICCPs which has to be sought at the level of the choriocapillaris.

INTERMEDIARY FORMS OF PICCP

In addition to the cases that associate more than one clinical entity per patient, it is not rare to have intermediary forms that are difficult to classify within one or the other subset of PICCP. Either they have a hybrid presentation or they have the morphology of one disease and the evolution of another, such as APMPPE/AMIC with a disease course characterised with recurrences behaving like serpiginous choroiditis or there are atypical cases that cannot be classified within a determined subset but for which ICGA shows that the pathology is definitively situated at the level of the choriocapillaris. When a sufficient number of cases of an intermediary or non described form behaving similarly are gathered, this allows to describe a new entity which happened with a series of cases presenting as APMPPE/AMIC having a subsequent evolution more compatible wih serpiginous choroiditis first termed as AMPPiginous choroiditis6 and later described as relentless placoid chorioretinitis.7 In this report of 6 patients the acute retinal lesions were similar to APMPPE or serpiginous choroiditis but had a prolonged progressive course and widespread

Figure 2A: Fundus photography OS at the stage when the clinical picture was typical of serpiginous choroiditis but progression did not respond to immunosuppressive therapy

distribution of lesions.7 Along the same line of evidence, Gupta and colleagues, in one of the largest series of serpiginous choroiditis reported so far indicate that in their part of the world all cases having the initial features of APMPPE showed progression resembling serpiginous choroiditis during follow-up20. We recently saw several patients first diagnosed as APMPPE/AMIC and subsequently evolving as serpiginous choroiditis, that were treated with immunosuppressants not that did not stop relentless progression. When thorough investigations were done to search for tuberculosis, gamma-interferon releasing assays were always positive and the disease was arrested with the adjunction of antituberculous therapy (Figure 2A-D).

Figure 2D: After introduction of triple antituberculous therapy a substantial improvement of visual fields was obtained form top to bottom; RE = right column of visual fields; LE = left column

Figures 2A-D: Serpiginous choroiditis related to tuberculosis initially diagnosed as APMPPE/AMIC

UNCLASSIFIABLE PRIMARY INFLAMMATORY CHORIOCAPILLAROPATHIES

The spectrum of PICCPs involves the choriocapillaris in diverse fashions and diverse degrees of severity and even when the entity seems to be defined it is important to perform a close ICGA guided follow-up as behaviour can be different from case to case. Moreover, in our series of more than 50 inflammatory choriocpillaropathies, nearly half cannot be classified into one of the well determined entities or evolve in an atypical way. It is also dangerous to make a definite diagnosis and blindly follow the treatment recommendations. This was the case with a patient that was diagnosed as APMPPE/AMIC on the base of ICGA an received no therapy resulting in macular atrophy of the left eye (Figure 3A). A few weeks later a decrease of visual acuity with photopsias occured in the right eye and the same diagnosis of APMPPE/ AMIC was given without therapeutical intervention resulting in a bilateral visual acuity of 0.1. The patient was seen at that time showing bilateral macular

Figure 3A: Unilateral choriocapillaris nonperfusion OS (top) shown by ICGA with no involvement OD (bottom)

atrophy (Figure 3B). ICGA showed inactive atrophy OS but still active disease OD (Figure 3C) with some of the lesions responding to systemic corticosteroids (Figure 3D). This case was not typical of APMPPE/ AMIC as involvement of the first eye went to the healing stage before the disease started in second eye. The recovery of some of the active areas after corticosteroid therapy in the right eye (Figure 3E) indicates that the disease was responsive to corticosteroid therapy. The key to apropriate management for both well determined entities and unusual forms of PICCPs is close functional and ICGA follow-up and introduction of inflammation suppressive therapy if necessary.

Evolution of unclassifiable forms is absolutely unpredictable. An example of benign ocular evolution is the case of a patient in his thirties hospitalised in a toxic state with very high fever of unknown origin. A total body scan was negative. When the patient complained of visal disturbance, ophthalmic examination showed full vision, no fundus abnormalities (Figure 4A), faint areas of faint retinal staining and discreet disc hyperfluorescence on FA (Figure 4B), whereas ICGA showed a multitude of small areas of choriocapillary nonperfusion (Figure 4C) with no translation on the visual fields (Figure 4D). This case, although bilateral, was absolutely not typical for APMPPE/AMIC as no yellow discoloration was

visible on fundus examination probably because areas of nonperfusion were small and non confluent. On the other hand the case was not consistent with MEWDS as it was bilateral. The diagnosis of a choriocapillaropathy allowed to indicate to our colleagues of internal medicine that the systemic disease was probably a viral disease that was also at the origin of the ocular findings. Evolution was favourable within a few days for the systemic disease and within several weeks for ocular disease that left no sequelae.

PRACTICAL ATTITUDE WHEN PRIMARY INFLAMMATORY CHORIOCAPILLAROPATHIES (PICCP) IS SUSPECTED

As a first step the characteristic ICGA patterns for primary inflammatory choriocapillaropathies (PICCP)

should be identified and the FA signs should be recorded to stage the severity of the involvement (strong versus mild choriocapillaris ischaemia). Before the diagnosis of PICCP is retained, an infectious cause, a neoplastic process or a systemic vasculitis causing choroidal ischaemia have to be excluded. The two most frequent infectious causes that can mimic a PICCP are syphilitic and tuberculous chorioretinitis. The neoplastic cause that has to be excluded is intraocular lymphoma and any systemic vasculitis, in particular systemic lupus erythematosus, can cause choroidal ischaemia. On the other hand it is easy to exclude central serous chorioretinopathy that produces choroidal hyperfluorescence and not hypofluorescence on ICG angiography.

Finally it is useful to try to classify the case into any of the known entities (MEWDS, APMPPE, multifocal

choroiditis, etc) in order to anticipate evolutionary patterns and determine a therapeutic approach (monitoring only versus therapeutic intervention using corticosteroid and/or immunosuppressive therapy). In case of severe visual impairement, even if the condition is known to recover spontaneously such as APMPPE, corticosteroids with or without immunosuppressants should probably be given as it is not known whether a well known entity is not going to develop into an atypical intermediary form possibly more deleterious to the chorioretina than initially anticipated.

CONCLUSION

Primary inflammatory choriocapillaropathies are caused by an inflammatory lesional process producing

disturbance in the perfusion of the choriocapillaris and functional disturbance in the outer retina.1-5,10,21, 22, 23 The lesional pattern of nonperfusion is different from one PICCP disease to the other producing benign conditions at one end of the spectrum such as MEWDS and deleterious conditions on the other end of the spectrum such as serpiginous choroiditis, with numerous intermediary forms including well-described entities and unclassifiable cases as well as an association of different entities. The factor determining the behaviour of each type of PICCP is not known but probably has to do with the level and severity of vasculopathy at the pre-choriocapillaris or the choriocapillaris level. Although the precise inflammatory scenario is not known, we now know what structure is primarily involved and we have now the means with