A progressive and non-infectious posterior uveitis, serpiginous choroiditis is rarely seen in ophthalmology clinics and is even rarer in optometry clinics. By chance, the patient I describe here was recommended to visit my practice to see if I could throw any light on their condition.
Never having encountered the condition previously, I decided to research the condition so that I could, if possible, offer informal advice and perhaps some hope and support – she had been given the impression that she would eventually become blind in both eyes. All the gadgets came out to play, including Optomap (wide field scanning laser ophthalmoscope), OCT and the Diopsys (electroretinography and visual evoked response) so as to build a picture on this rare condition.
Case
Female patient VS, aged 61, had noticed visual difficulties in her left eye. Her then optometrist was at a loss to explain this and had referred her to an ophthalmologist. Various tests were undertaken by a local ophthalmologist and eventually she was referred to Moorfields in London. Within a year, she had near total loss of vision in the left eye, a drop from 6/9 to count fingers at 10cm.
She was prescribed oral steroids and immunosuppressants but the vision loss was rapid in the left eye and a diagnosis of serpiginous choroiditis was confirmed. She was not keen on the treatment with steroids so this was halted and regular three monthly check ups were scheduled.
Ocular examination:
R. +1.25 / -3.50 X 180 (6/9) ADD +2.50DS N5
L. +1.25 / -4.50 X 2 (count fingers at 10cm)
- Intra ocular pressures within normal range R & L.
- Right optic nerve and peripheral retina healthy (figure 1).
- Right macula with OCT showed an exudate and cystoid changes (graded as maculopathy grade 1) although she was not diabetic.
- Left eye showed peripapillary atrophy and multiple white dots (figure 2).
- Left eye macula showed complete atrophy and there was slight sub-retinal fluid inferior to the fovea giving inferior thickness of 389 microns.
Figure 1: Right eye OCT angiography showing exudates at the macula. Author has superimposed the thickness map showing 365 microns over the OCT to emphasise the cystoid changes and exudates within the outer retina. There is a suggestion of a central inflammatory response
Diopsys ERG & VEP testing
1 Contrast sensitivity pattern ERG (figure 3) revealed left eye magnitude delay to magnitude ratio outside the normal at 0.57 indicating a low contrast large magnocellular retinal ganglion cell dysfunction in the left eye.
Figure 2: Left retinal image showing peripapillary atrophy along with geographical atrophy at the macula as a result of serpiginous choroiditis. The angiography image suggests extensive capillary loss centrally. The thickness map shows normal central retinal thickness. The OCT image shows oedema inferior to the fovea possibly due to subretinal leakage and this correlates with the thickness map (arrows). This might be neovascularisation or an inflammatory response
2 Concentric stimulus field pattern ERG (figure 4) of the left eye revealed both the magnitude delay and magnitude delay/magnitude ratio was very low at 0.11 and 0.09, indicating a high contrast parvocellular small retinal ganglion cell dysfunction.
3 Contrast sensitivity and concentric stimulus field pattern ERG in the right eye revealed normal magnitude delay to magnitude ratio of 0.87 and 0.79 respectively indicating no magnocellular or parvocellular retinal ganglion cell dysfunction.
Figure 3: Contrast sensitivity pattern ERG for the left eye
4 VEP measurements revealed abnormal VEP response in the left eye (figure 5). VEP measures the conduction integrity of the entire visual pathway ganglion axons from the retina, optic nerve, chiasma, optic radiation and the visual cortex. In the left eye the P100 was not identifiable indicating there were no response from the ganglion axons which would provide the amplitude P wave and the response which would normally take 100ms was once again unobtainable.
Figure 4: Concentri stimulus field pattern ERG for the left eye
5 Bothe the fixed luminance flicker test (figure 6) and the multiple flicker luminance test (figure 7) showed asymmetry and a weaker left eye response.
6 The right eye VEP showed a good amplitude to high and low contrast and latency of 111.3ms to high contrast and 109.4ms to low contrast stimuli (close to 100ms applicable to normal VEP latency). The high and low contrast response indicates both the parvocellular and magnocellular pathway were normal. The magnocellular ganglion cells convey motion and low contrast black and white visual information while the parvocellular ganglion cells convey colour, texture and depth information.
Figure 5: VEP results for left eye. A major positive peak normally occurs at 100 ms and the so-called P100 indicates the time the electrical signal takes to travel from the retina to the visual cortex and the conduction integrity of the myelin sheath. Lowering the contrast increases the latencies, especially with disease affecting the optic nerve such as multiple sclerosis
Serpiginous Choroiditis
In 1900, an English ophthalmologist and dermatologist described serpiginous choroiditis as ‘a unique pattern of creeping progression of choroidal inflammation with active borders and, when healed, has the appearance of the borders of a continent in a map’. The creeping or snaking of the inflammation gives the name serpiginous. White dot syndromes are conditions that involve inflammation of the retina and lymphocytic infiltration of the choroid and serpiginous choroiditis is one within this group.
Figure 6: Multiple luminance flicker tracks changes in retinal function even in the presence of media opacities
Serpiginous choroiditis is a rare, idiopathic and progressive geographic pattern of choroiditis affecting two layers namely the choriocapillaries and retinal pigment epithelium and usually extending from the juxtapapillary (near optic nerve head) choroid and intermittently spreading centrifugally. It is an asymmetric bilateral condition.
It is characterised by multiple, confluent foci of exudates and scar formation, especially in the choroid. Fluorescein angiography and histological studies have revealed loss of both the choriocapillaris and the retinal pigment epithelium.
Figure 7: Fixed luminance flicker test measures the effect of retinopathies on vision, even in the presence of media opacities
Serpiginous choroiditis is generally asymptomatic until vision becomes affected due to either direct inflammatory damage to the macula or secondary choroidal neovascular membrane formation. Painless loss of acuity, blurred vision, metamorphopsia, photopsia and visual field scotomas are classic symptoms.
Figure 8: Autofluorescence image on the left showing hyperfluorescence indicated by the bright spots and suggestive of chorioretinal inflammation. The macular image in the centre shows cystoid maculopathy (405 microns) while the angio image shows dark areas of capillary malfunction. The image on the right shows resolution of the inflammation following a steroid implant and there are fewer areas of hyperfluorescence. There is minimal cystoid maculopathy (365 microns) and an area of RPE atrophy depicted by darker area on the autofluorescent image. The capillary network in December appeared to be back on track with no obvious capillary loss
Roughly 90% of patients with untreated serpiginous choroiditis have macular involvement. Around 30% of patients have exclusively macula serpiginous choroiditis, where there is no peripapillary choroidal or geographic atrophy. The absence of atrophy initially makes this condition difficult to diagnose.
The serpiginous choroiditis disorder has two stages:
1 Acute stage, during which the lesions develop and may spread. Acute lesions appear greyish yellow with distinct borders and may last weeks to months.
2 Chronic stage, during which the lesions do not progress but the inactive lesions lead to scarring, atrophy and pigmentary clumping. Recurrence can occur in the scar tissue left by the old lesions. Choroidal neovascularisation occurs in 25% of patients with subretinal fluid and haemorrhaging.
Figure 9: Left eye autofluorescence revealing areas of photoreceptor and RPE loss seen as dark patches. The blue arrow and arc show some hyperfluorescence indicative of inflammation or active disease
Epidemiology
Serpiginous choroiditis is found in less than 5% of posterior uveitis cases and is most likely in middle age men. There is no familial or ethnic predilection. The average age of presentation is from 43 to 59 years, and no systemic disease association has been identified. The actual prevalence of serpiginous choroiditis is unclear, and complicated by geographical variation. For example, there has been no single case reported in Los Angeles while in the rest of California there were reports of 2.7% of patients referred to uveitis clinics. In India, serpiginous choroiditis represented 18.9% of posterior uveitis cases and this could be due to the inclusion of tuberculosis choroiditis which may mimic serpiginous choroiditis. In areas where tuberculosis is not endemic, the cases of serpiginous choroiditis varies from 1.6% to 5.3%.
Pathology
Serpiginous choroiditis is thought to be an immunological condition because it responds to immunosuppressants and corticosteroids, but the triggering event for this localised inflammatory response remains unclear. Also, the higher frequency of HLA-B7, HLA-A2, HLA-B8 and HLA-Dw3 in patients with serpiginous choroiditis compared to the general population may suggest an underlying, genetically predisposed autoimmune process. Human leukocyte antigen complex, HLA-B, is a human gene that provides instruction for making proteins that plays a critical role in the immune system.
Medical therapy
Treatment of serpiginous choroiditis is to contain the advancing chorioretinal inflammatory lesions threatening the fovea. Steroid sparing therapy using low dose azathioprine, cyclosporine and prednisolone in combination is commonly used. Weaning off from steroids, cyclosporine and azathioprine (in this order) reduces the individual side effects of each drug because of the low dosage compared to single treatment. It is also thought that triple therapy shortens the duration of the acute lesions and prevent recurrence. Long term management can be challenging, and up to 25% of the eyes have a final visual acuity of less than 6/60.
A prolonged course of immunosuppression is given with a very slow taper to avoid recurrence and patients need to be carefully monitored.
Differential diagnosis
Two conditions that mimic serpiginous choroiditis (SC) are:
1 Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) – Patients with APMPPE are relatively young compared to middle aged SC patients. APMPPE precedes viral infections, and lesions rarely recur. There is a better visual outcome as choroidal atrophy and scarring is minimal. Lesions with APMPPE heal in seven to 14 days while SC lesions resolve over three to six months or may take longer.
2 Tuberculosis (TB) – TB represents a hypersensitive reaction to infection with the mycobacterium Tuberculosis leading to a chorioretinitis which is similar in presentation to SC. TB lesions are thought to be more peripheral and multifocal and do not border around the optic disc. They also spare the macula. TB lesions also demonstrate a significant vitritis (leaking of inflammatory cells into the posterior chamber) which is absent in serpiginous choroid. TB choroiditis sufferers should be screened, whether they are from TB endemic areas or not, and suspect cases need to be confirmed with the Tuberculin skin test or the QuantiFeron – TB Gold blood test to see if the patient is exposed to this very contagious Tuberculosis bacterium.
Other conditions that show similar choroidal atrophy and scarring are myopia, sarcoidosis, toxoplasmosis and choroidal metastatic tumours.
Conclusion
It was interesting to monitor this patient, with no iritis or vitritis and the only symptoms being visual blurring and an extended blind spot due to optic nerve involvement. It is unfortunate that the patient had refrained from treatment as all the studies show that treatment with triple combination therapy slows the progression of the lesions and prevents recurrence. There is also a high risk of the second eye being involved within five years without treatment. It is interesting to note that the unaffected right eye has cystoid maculopathy and exudates within the retina with no diabetes noted in this patient. Is it a red herring, some sort of inflammatory process occurring within the retina, or could it be secondary diabetic hyperglycaemia due to immunosuppression side effects?
Sting in the tail
In 2017, the patient rang in a panic to say her good eye, the right eye, appeared very blurred. Ophthalmic examination confirmed that acuity had reduced to 6/18 from the 6/9 achieved just six months earlier. Fundus examination revealed serpiginous choroiditis from the nasal aspect of the macula to the optic disc. She was referred immediately to Moorfields Eye Hospital and I have summarised the results of the findings and the treatment in figure 8.
The treatment was with steroid implant injected to the right eye and fortunately eight months down the line there are positive results with the inflammation gone.
I have used fundus autofluorescence (FAF) to illustrate the accuracy in detecting non-invasively early disease activity and extent of retinal pigment epithelium (RPE) damage (figure 9).
It is thought that retinal inflammation activates blood-borne macrophages and T-cells in the retina generating toxic agents which cause photoreceptor mitochondrial protein dysregulation and cell death. Lipofuscin, a degraded photoreceptor outer segment by-product, accumulates in the RPE cystol leading to oxidative RPE cell death and photoreceptor loss. Lipofuscin is a fluorescent pigment so when excited with short to medium wavelength visible illumination will exhibit emission of light at higher wavelength from 500-730nm.
With inflammation, there is an increased metabolic activity of the RPE and hence there is hyperfluorescence (bright spots) while there is darkening or hypofluorescence indicating decrease in FAF due to loss of photoreceptors or RPE as the inflammation subsides.
I hope this case is both interesting for the disease itself, but also to illustrate the value of the variety of imaging and testing options now available to optometrists allowing a more informed patient management.
Kirit Patel is an optometrist in independent practice in Radlett, Hertfordshire.