Retrospective Review of Pediatric Thyroid Eye

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REVIEW

Retrospective Review of Pediatric Thyroid Eye Disease Cases Referred to Nicklaus Children's Hospital  Enghelberg M1  Wong A1  Aguilera ZP1,2  Warman R1,2

 Email: -

 Department of Ophthalmology, Larkin Community Hospital, South Miami, FL - USA. 2  Department of Ophthalmology, Nicklaus Children’s Hospital, South Miami, FL - USA.

 Date of submission: : 23/05/2018

1

 Funding: None  Proprietary/financial interes: None  Date of approval: 18/06/2018

Corresponding author: Moises Enghelberg, DO Department of Ophthalmology, Larkin Community Hospital 7031 SW 62nd Ave, South Miami, FL 33143, USA Phone: +1 305-284-7500

Abstract Purpose: We evaluate presenting features and treatment options of pediatric thyroid eye disease, and discuss the morbidity of this condition in the pediatric population. Methods: A retrospective chart review of 11 patients referred for evaluation of thyroid eye disease at a pediatric tertiary care facility in Miami, Florida. Results: The average age at presentation was 12.7 years. The most common ocular complaint was mild irritation. The average displacement on Hertel exophthalmometry was 21 mm for the right eye, and 21.45 mm for the left eye. Lower scleral show was the most common eyelid finding. Patients tended to be positive for thyroid stimulating immunoglobulin and thyroid peroxidase antibody. Conclusion: In contrast to thyroid eye disease in adults, the condition tends to present with mild ocular findings in children. Pediatric patients presenting with thyroid eye disease respond very well to medical therapy aimed at enhancing the altered ocular surface. Keywords: thyroid eye disease; proptosis; Graves' Disease; lower scleral show.

Introduction Less common in children than it is in adults, thyroid eye disease (TED) occurs in 0.79 to 6.5 per 100,000 children annually, with greater frequency in females, in those with concurrent autoimmune disorders or with a family history of autoimmune thyroid disease, and in those of Chinese

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ancestry.1-3 As in adults, TED is most often associated with acquired hyperthyroidism, but may occur in hypothyroid and euthyroid states as well.4 One-third of children with Graves’ disease develop ophthalmopathy, with a median time of one month from diagnosis of Graves’ disease until development of TED, although 82% of children had ocular complaints prior to being diagnosis in a study by Jarusaitiene et al.2,5 Two-thirds of children with TED are between the ages of 11 and 18 years, presumably due to an increased prevalence of smoking in this age group.2 Although postpubertal children seem to experience more serious complications, signs of TED are generally mild and self-resolving, potentially delaying diagnosis.1,4 Common manifestations noted in the literature include upper eyelid retraction, proptosis, eyelid lag, pain, foreign body sensation, photosensitivity, tearing, and diplopia, while optic neuropathy and corneal breakdown are infrequent.4 In addition, myopia may accompany proptosis.4 In contrast to children, adults with Graves ‘ophthalmopathy seem to experience more severe disease manifestations, with higher rates of exophthalmos, restrictive myopathy, and optic nerve dysfunction.3

Methods We performed a retrospective chart review of children with Graves’ ophthalmopathy who had been referred for ophthalmic evaluation at Nicklaus Children's Hospital, a tertiary care center in Miami, Florida. We selected our patients based on diagnostic ICD-9 codes. Since the aim of the study was to further characterize the manifestations

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of TED, patients whose ocular exams did not exhibit findings consistent with TED were excluded. Each patient’s sex, age, systemic symptoms, thyroid autoantibody results, best corrected visual acuity (BCVA), visual field results, stereoacuity, Ishihara color plate results, motility, Hertel exophthalmometry measurements, external and biomicroscopy findings, ocular symptoms, treatment, and thyroid disorder were documented, and most of the results were averaged.

Results We identified a total of 55 patients with Graves’ disease who had been examined by the endocrinology team in the last decade. Of this cohort, 15 patients had ocular complaints that prompted referral to the pediatric ophthalmology service. Only 11 of these 15 patients exhibited signs of TED, and were included in this case series.

Table 1 – Children with Graves’ ophthalmopathy Patient

Demographic Information

Systemic Symptoms

Exophthalmometry

Antibodies

Ocular Symptoms

Visual Acuity

Visual Fields

40 seconds of arc

CP

Female, 8 years of age

not recorded

base 90: 16mm OD and 20mm OS

data unavailable

mild irritation

-1 abduction OD, -1 adduction -1/2 abduction left eye

AM

Female, 4 years of age

tremor, tachycardia, diarrhea

base 90: 20mm OU

TSI +

none

E'X 20 - full

40 seconds of arc

EL

Male, 19 years of age

tremor, tachycardia/ palpitations

base 100: 19mm OD, 20mmOS

data unavailable

none

ortho

not recorded

YB

Female, 19 years of age

tremor

base 95: 25mm OU

data unavailable

ortho

40 seconds of arc

JC

Female, 19 years of age

not recorded

base:90 19mm OU

data unavailable

irritation

ortho

40 seconds of arc

JO

Female, 14 years of age

suicide attempt, anxiety

base 98: 21mm OU

TSI +

none

ortho

not recorded

CH

Female, 15 years of age

tachycardia, diarrhea, weight loss

base 100: 22mm OU

Tg Ab +, TPO +

none

ortho

40 seconds of arc

CS

Female, 14 years of age

tremor

base 95: 22mm OU

TSI +, TPO +, Tg Ab +

none

-1/2 abduction OU

40 seconds of arc

Female, 11 years of age

weight loss, tremor, anxiety, shortness of breath

base90: 22mm OU

TPO Ab +, TBII +,Tg Ab +

itching/burning/ blurry vision

ortho

not recorded

MR

Female, 11 years of age

weight loss, anxiety, polydipsia, polyuria

base 110: 26mm OD 25.5 OS

TSI +, TrAB

mild irritation, burning

ortho

not recorded

LR

Female, 12 years of age

weight loss, sleepiness, tachycardia

base 110: 19mm OD 19.5 OS

TPO +, Tg Ab +

irritation

ortho

not recorded

30% mild irritation

18% presented with motility

20/20 on average

CS

12.7 years on average

45.4% tremor

21 OD - 21.45 OS

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36.3%TPO, TSI 36.3%

none

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Retinoscopy

External and Biomicroscopy Findings

Treatment

Diagnosis

CP

plus 0.75 OU

lax outer canthus, and retraction of the lower eyelids, + eyelid lag, +1conjunctival injection

methimazole, laters received radioactive iodine and supplmented with synthroid, s/p I131

Graves' Disease

AM

plus 0.25 plus 1.75x90 - plus 50 plus 1.25x91, corrects to 20/20 OU

lower scleral show, 2mm lid lag and retraction, OU

methimazole

Graves' Disease

EL

plano +0.50x90

left lower scleral show - subtle

methimazole

Graves' Disease

YB

plus 4.75 +0.75 160 OU

lower scleral show

not recorded

Graves' Disease

JC

plano

lower scleral show

not recorded

Graves' Disease

JO

not recorded

lower scleral show, + eyelid lag

thyroid resection

Graves' Disease

CH

plus 0.25 +0.25 t 90

lower slceral show, 2mm

thyredectomy, methimazole, atenolol

Graves' Disease

CS

-2.00+0/50 x 35 OD / -2.0

mild proptosis, +1 hyperemia over medial rectus

thyredectomy, methimazole, atenolol

Graves' Disease

CS

not recorded

lower scleral show, eyelid retraction

thiamazole

Graves' Disease

MR

-0.75+0.50x065 OD - 0.75

exposure keratopahy, proptosis

propranolol + RAI

Graves' Disease

plus0.25 and -0.25

mild scleral show 0.5mm, and lagophthalmos of 1mm and mild proptosis

propranolol and methimazole

Graves' Disease

Patient

LR

Table 1 – Children with Graves’ ophthalmopathy

The baseline ocular examination findings are displayed in Table 1. The average age of presentation in our series was 12.7 years. Most of the patients were females, constituting 90% of the study group. The most common systemic complaint was a fine tremor. Diarrhea, weight loss, anxiety, and tachycardia were also heavily present throughout the study population. One patient presented with suicidal ideation. The most common ocular complaint was itching and mild irritation, with over 30% of patients expressing these symptoms. The vast majority of patients did not complain of visual disturbances, and 82% had a BCVA of 20/20 in both eyes. Average refractive error by retinoscopy was +0.44 +0.70 x 88.33 OD and +0.41 +0.68 x 107.75 OS. One child with exposure keratopathy had a BCVA of 20/50, while another child with intermittent exotropia had a BCVA of 20/50 in one eye and a BCVA of 20/20 in the fellow eye. All patients presented with lower scleral show Figure 1, with one patient developing exposure keratopathy. Superior eyelid retraction was present in 18% of patients, and another 27% presented with eyelid lag on downgaze. The average displacement on Hertel

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exophthalmometry was 21 mm for the right eye, and 21.45 mm for the left eye. In addition, 18% of patients presented with hyperemia over one of the extraocular muscles. A minority of cases, constituting 18% of the study cohort, presented with slight limitation of abduction. One patient presented with an unre-lated intermittent exotropia. Available laboratory findings are displayed in Table 1. Of the seven patients who had thyroid autoantibody studies available, four (57%) were positive for thyroid peroxidase (TPO). Thyroid stimulating immunoglobulin (TSI) titers were also positive in 57% of patients. It is important to note that there was considerable overlap between antibody titers, with five of the seven patients (71%) being positive for two or more thyroid auto-antibodies. Approximately 90% of patients presented with low TSH. Treatment plans for nine patients were available Table 1. Of these nine patients, 78% were treated with either methimazole or thiamazole. Three patients (33%) underwent thyroidectomy, while two patients (22%) actually received radioactive iodine. Four patients (44%) were also treated with beta blockers. All patients received topical lubricants since lower scleral show was such a

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Figure 1A. E  xternal color photograph of patient JO demonstrating lower scleral show with a small degree of bilateral proptosis.

Figure 1B. External color photograph of patient EL with lower scleral show and proptosis of the left eye.

Figure 1C. E  xternal color photograph of patient CP with lower scleral show bilaterally.

prevalent finding, and all five patients who presented with complaints of itching and irritation experienced subjective improvement, as well as decreased punctate epithelial erosions after instillation of fluorescein.

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Discussion In Jankauskiene and Jarusaitiene’s retrospective study of 18 children with TED second-ary to Graves’ disease, the clinical activity score (CAS) based on inflammatory ocular symptoms was generally mild.1 In their study, 72.3% of children had upper eyelid retraction, 66.7% had proptosis, and 44.4% had eyelid lag. Our results exhibited a comparable incidence of proptosis (54%) and eyelid abnormalities (100%), though lower scleral show secondary to proptosis or lower eyelid retraction was our most common adnexal finding. In comparison, Chan et al reported proptosis in only 12.0% of 83 children studied.3 Similar to our study however, restrictive ex-traocular myopathy was an uncommon finding, exhibited in only 1.2% of children in their study, and they reported no cases of optic nerve dysfunction.3 Two children (18%) in our case series displayed mild ocular motility disturbances secondary to TED, and none displayed evidence of optic nerve dysfunction. In contrast to the typically mild findings of Graves’ ophthalmopathy in children, proptosis can be found in up to 60.8% in adults, while restrictive myopathy and optic nerve dysfunction have been reported in 42.5% and 5.8% of adults, respectively.3 The most common ocular complaints in our study were itching and mild irritation, which we believe to be secondary to increased corneal exposure caused by inferior scleral show and mild proptosis. Mild and moderate ocular surface symptoms respond excellently to topical lubrication, as demonstrated by Goldstein et al in their study of the course of pediatric TED and its most common findings in 26 children.8 We found therapeutic results similar to those of Goldstein et al with resolution of these symptoms in all children who received topical lubrication. Positive TSI titers, which have been shown to be associated with development of TED in adults, also correlated with the development of TED in children in a study of 49 patients with Graves’ disease by Acuna et al.6 Fifty-seven percent of our patients presented with positive TPO antibodies, while another 57% presented with positive TSI titers in our study. Shibayama et al found that TSI levels in children with TED were not significantly different from those without TED however, and instead found a strong correlation between TED and higher thyrotropinbinding inhibitory immunoglobulin (TBII) levels in their study of 35 serum samples from chil-dren with untreated active Grave’s disease.7 We did not evaluate TBII titers in our cohort.

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Diagnosis of pediatric TED is based on ocular manifestations and evidence of thyroid autoimmunity. Even though the orbital fat tends to be more involved in this age group, orbital MRI may be helpful for detection of extraocular muscle inflammation.4 The typical treatment of Graves’ disease in children is two years of antithyroid therapy, such as with methimazole, followed by re-evaluation and monitoring thereafter.1 Radioiodine is a treatment option as well, but its use in children less than five years of age can increase risk of thyroid cancer; retrobulbar irradiation is also contraindicated due to risk of malignancy in children.4 Thyroidectomy can generally improve ocular symptoms. Ocular manifestations typically resolve once a euthyroid state is established.4 With antithyroid treatment, 46.1-56.6% of Asian children are able to achieve remis-sion, compared to 12-33% of children in other studies.1 Corticosteroids, somatostatin analogs, and immunomodulatory therapy may be necessary if symptoms do not improve even in the pres-ence of a euthyroid state.4 The majority of patients

in our study were treated with an antithyroid drug, while 33 underwent thyroidectomy, and two patients, ages 8 and 11, were treated with radioactive iodine.

Conclusion Compared to the adult disease course, pediatric TED demonstrates much more benign manifestations, and restrictive strabismic patterns and optic nerve dysfunction are much less common in pediatric TED than it is in adult TED. The most prevalent findings in our study of 11 children with pediatric TED were lower scleral show, mild to moderate ocular surface disturbances, and a small degree of proptosis. Symptoms of ocular exposure in children are amenable to lubrication and conservative medical measures. Treatment plans of most children in our study included antithyroid therapy. Children’s symptoms tend to regress after an adequate thyroid status is achieved. 

References 1. Jankauskiene J, Jarusaitiene D. The Influence of Juvenile Graves' Ophthalmopathy on Graves' Disease Course. J Ophthalmol. 2017;2017:4853905. 2. Krassas GE, Segni M, Wiersinga WM. Childhood Graves' ophthalmopathy: results of a Eu-ropean questionnaire study. Eur J Endocrinol. 2005;153(4):515-21. 3. ChanW,Wong GW, Fan DS, Cheng AC, Lam DS, Ng JS. Ophthalmopathy in childhood Graves' disease. Br J Ophthalmol. 2002;86(7):740-2. 4. Szczapa-jagustyn J, Gotz-więckowska A, Kocięcki J. An update on thyroid-associated oph-thalmopathy in children and adolescents. J Pediatr Endocrinol Metab. 2016;29(10):1115-22. 5. Jarusaitiene D, Verkauskiene R, Jasinskas V, Jankauskiene J. Predictive Factors of Devel-opment of Graves' Ophthalmopathy for Patients with Juvenile Graves' Disease. Int J Endocrinol. 2016;2016:8129497.

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6.  Acuna OM, Athannassaki I, Paysse EA. Association between thyroid-stimulating immuno-globulin levels and ocular findings in pediatric patients with Graves disease. Trans Am Ophtha-mol Soc. 2007;105:146-50. 7. Shibayama K, Ohyama Y, Yokota Y, Ohtsu S, Takubo N, Matsuura N. Assays for thyroid-stimulating antibodies and thyrotropin-binding inhibitory immunoglobulins in children with Graves' disease. Endocr J. 2005;52(5):505-10. 8. Goldstein SM, KatowitzWR, MoshangT, Katowitz JA. Pediatric thyroidassociated orbitop-athy: the Children's Hospital of Philadelphia experience and literature review. Thyroid. 2008;18(9):997-9.

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Optical Coherence Tomography with Angiography in Behçet Uveitis  Diana Silva, MD  Ana Sofia Lopes, MD  Luísa Colaço, MD  Maria Lisboa, MD  Sara Pinto, MD  Manuela Bernardo, MD  Filomena Silva, MD  Isabel Prieto, MD  Department of Ophthalmology, Hospital Prof. Dr. Fernando Fonseca E.P.E., Amadora, Portugal

Abstract Purpose: Behçet uveitis is a cause of retinal vasculitis, with fluorescein angiography being the gold-standard diagnostic exam. Optical coherence tomography with angiography (OCT-A) is a non-invasive exam that analyzes macular retinal circulation with high resolution, and therefore, could be a useful diagnostic exam in these patients. Material and methods: Analysis of 14 eyes of 8 patients with Behçet uveitis from our institution that were examined by OCT A (AngioPlex®, Zeiss). Macular morphology, area, perimeter and circularity of the foveal avascular zone, as well as central internal and global macular vascular density were evaluated. We compared our results with healthy controls. Results: Mean visual acuity in the patient’s subgroup was 0,84±0,25 and 3 eyes had previous diagnosis of retinal vasculitis with fluorescein angiography. Morphologically we found attenuation of the superficial and deep capillary plexus in 8 eyes, and in 1 of these eyes atrophy of the internal retinal layers was also found in a localized territory. In the foveal avascular area, no statistically significant changes were observed in its area and perimeter (p=0.804 and p=0.380 respectively), although we did find significant changes in its circularity (p=0.027). Vascular density was significantly altered in the internal (p=0.023) and global (p=0.028) macular parameters. Conclusion: We found changes in the macular microcirculation in patients with Behçet uveitis, even in the absence of angiographic changes. Future studies with more patients are necessary to understand the clinical significance of these changes. VISION PAN-AMERICA | JUL -SEP 2018 | VOL. 17 (3)

Corresponding author address: Diana Silva, MD Praceta Papa João XXI, 1, 2º esquerdo, 2685-217 Portela  Phone: + 351 969743535  Email: [email protected]  Funding: None  Proprietary/financial interest: None  Date of submission: 15/07/2018  Date of Approval: 12/09/2018

Keywords: Angiography; Behçet uveitis; foveal avascular zone; Optical Coherence Tomography angiography; vascular density.

Introduction Behçet uveitis is a chronic autoimmune vasculitis with multi-systemic involvement and unknown etiology.1 Ocular involvement may be present in up to 70% of cases.1,2 Prominent manifestations include retinal vasculitis, occlusive or non occlusive periphlebitis, the presence of retinal infiltrates and optic disc edema.1 Fluorescein angiography is the gold-standard method for evaluation and monitoring of retinal vasculitis in Behçet uveitis patients, revealing contrast diffusion throughout affected vessels, while also facilitating the detection of other retinal alterations such as ischemia, neovascularization and cystoid macular edema, among others. Although of unquestionable clinical value, fluorescein angiography is a mildly invasive exam requiring a dye, which might constitute a limitation in some patients. Light dispersion phenomena also limit the exam’s resolution.3 Optical coherence tomography angiography (OCT-A) is a recent noninvasive imaging method that allows imaging of retinal and choroidal microvascularization without requiring contrast. The method is based on detecting fluctuations of red blood cells’ signal in successive B-scan images obtained in the same location.4,5 Multiple works have shown the clinical utility of this diagnosis method in diseases such as age-related macular degeneration, diabetic retinopathy, retinal occlusive venous/arterial disease, and sickle-cell retinopathy.6-18 However, there is a limited number of recently published studies (Somki-

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jrungroj et al. 2017 e Khairallah et al. 2017)19,20 that have analyzed Behçet uveitis patients with the OCT-A, finding alterations in macular perfusion in the superficial, and deep retinal plexus. The goal of our study is to study retinal microvasculature at the macular level using OCT-A on a population of Behçet uveitis patients from our institution’s ophthalmology clinic.

Methods Our study complies with the principles of the Declaration of Helsinki, and informed consent was obtained from all patients. This is a retrospective study, where we included patients previously diagnosed with Behçet uveitis (according to the international criteria of Behçet uveitis’s international consensus) 21 under ophthalmology follow-up in our institution. Patients with high refractive error (>5D spherical equivalent), posterior capsule opacification, and history of retinal disease or Diabetes Mellitus were excluded. Clinical records (n=11) were consulted for best recorded corrected visual acuity (BCVA), previous ocular involvement pattern, the timeline of the disease’s evolution, the disease’s activity and fluorescein angiography findings in the last 6 months. All the patients that we included did not have active uveitis in the last 6 months, to avoid limitations associated with imaging associated with anterior segment and vitreous inflammation. Among the 11 eligible patients called for OCT-A, only 8 attended. It was only possible to perform the exam in 14 eyes, due to counting fingers vision in 2 eyes, therefore excluding the findings of these eyes. Every patient underwent a routine ophthalmic exam. We performed OCT-A with the CIRRUS™ HD-OCT Model 5000 AngioPlex®, Zeiss machine. The machine is a spectral domain OCT working at a speed of 68,000 A-scans per second. Microvasculature images en face are obtained based on the OCT microangiography-complex algorithm, that takes into account variations in phase and intensity of sequential B-scans of the same location. We obtained images of the macular cube in the spectral domain OCT mode and images of a 3x3mm macular cube in the angiography mode. We analyzed the morphology of retinal layers regarding their structural integrity in the macular cube obtained by spectral domain. With the angiography mode images, we analyzed the scans from the superficial and deep capillary plexus that were measured automatically by the software. We searched for areas of disruption in the perifoveal capillary network, capillary alterations (thinning, dilation, shunts, telangiectasia), non-perfusion/hypoperfusion areas and localized or dif-

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fuse areas of disrupted capillary network architecture in the superficial or deep plexus’s. We performed quantitative analysis of the foveal avascular zone’s area, perimeter and circularity, as well as the central, internal and global macular vascular density, using the machine’s automated analysis software. A control group with a similar demographic profile also underwent the same evaluation. In the selection process, individuals with high refractive error (>5.0D spherical equivalent) or any ocular disease were excluded. Quantitative data were analyzed with IBM SPSS Statistics® (Version 2.2) software. Each studied parameter was tested for normality and subjected to a paired sample T-Test if normal, or Mann-Whitney’s test otherwise. Specifically, avascular foveal zone area and circularity were compared by Mann-Whitney’s test and the remaining analyses by paired sample T-Test. We calculated the correlation between visual acuity parameters, as well as disease duration, and avascular foveal zone area, perimeter and circularity, central, internal and global macular vascular density. The calculated correlation coefficient was Spearman’s rho.

Results The studied population and the control group were demographically equivalent with an average age of Behçet uveitis patients of 47.75±11.59, and 43.00±12.90 in the control group. The sex distribution in the Behçet uveitis patients was 8 females and 6 males, with the control group having 9 females and 5 males. Behçet uveitis patients had a best-corrected visual acuity of 0.84±0.25 in the Snellen visual acuity scale. Among the 8 patients, five were found to have had previous ocular involvement with posterior uveitis, three of which with retinal vasculitis/branch retinal vein occlusion identified by angiography (Table 1). The patients with posterior uveitis without retinal vasculitis had retinitis (2 cases) and papillitis (3 cases). Morphologic analysis of retinal layers found retinal atrophy in just 1 eye, affecting the internal retinal layers, corresponding to one of the eyes with retinal vasculitis (patient 7, Figure 1). Analysis of the 3x3mm macular cube revealed vascular rarefaction in the superficial and deep plexus in 8 eyes, 4 of which corresponding to patients showing previous ocular involvement with retinal vasculitis (Figures 2 and 3); the remaining 4 did not have an angiographic diagnosis of vasculitis.

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Table 1 – Characterization of the Behçet uveitis population Patient

Age

Eye

BCVA

Disease duration (years)

1

42

RE

1

13

Panuveitis

2

55

RE

0,8

13

Episcleritis

Negative

2

55

LE

0,8

13

Episcleritis

Negative

3

65

RE

0,8

35

Posterior uveitis

Glaucoma, Cataract

Negative

3

65

LE

0,8

35

Posterior uveitis

Glaucoma, Cataract

Negative

4

35

LE

1

11

Panuveitis + Vasculitis

Glaucoma, Cataract

Negative

12

Non granulomatous anterior uveitis, punctate keratitis

NA

NA

5

53

RE

1

Ocular involvement

Ocular complications

HLA B51

Glaucoma

Negative

5

53

LE

1

12

Non granulomatous anterior uveitis, punctate keratitis

6

34

RE

1

6

Non granulomatous anterior uveitis

Positive

6

34

LE

1

6

Non granulomatous anterior uveitis

Positive

7

38

RE

0,66

8

Panuveitis + Vasculitis

Negative

7

38

LE

1

8

Panuveitis + Vasculitis

Negative

8

60

RE

0,2

13

Panuveitis

Glaucoma, Cataract

Negative

8

60

LE

0,5

13

Panuveitis

Glaucoma, Cataract

Negative

Table 1 – Characterization of the Behçet uveitis population (RE-Right Eye, LE-Left Eye, BCVA-Best corrected visual acuity with the Snellen scale).

Average avascular foveal zone area measured at the superficial capillary plexus was 0.25±0.79mm2, average perimeter was 2.33±0.43mm and average circularity was 0.61±0.12. Comparing these parameters with the control group’s parameters, we found no statistically significant difference for the avascular foveal zone area (p=0.804) and perimeter (p=0.380). A statistically significant difference was found for circularity (p=0.027) (Table 2). Average central macular vascular density at the superficial capillary plexus was 11.60±4.17mm-1, average internal density was 19.97±3.50mm-1, and average global macular density was 19.13±3.23mm-1. We found statistically significant differences in the internal vascular density (p=0.023) and global vascular density (p=0.028), although not for the central vascular density (p=0.531) (Table 3). We did not find statistically significant correlations between visual acuity or disease duration and the quantitative parameters of the avascular foveal zone, namely area, perimeter, circularity, central, internal and global macular density (Table 4). VISION PAN-AMERICA | JUL -SEP 2018 | VOL. 17 (3)

Table 2 – Comparison of the foveal avascular area parameters in patients with Behçet uveitis and controls. Studied parameters

Behçet uveitis

Control

p value

Foveal avascular area

0.25±0.73

0.26±0.12

0.804

Foveal avascular zone perimeter

2.33±0.49

2.16±0.53

0.380

Foveal circularity

0.61±0.12

0.69±0.05

0.027

Table 2 – Comparison of the foveal avascular area parameters in patients with Behçet uveitis and controls.

Table 3 – Comparison of the macular vascular density in patients with Behçet uveitis and controls. Behçet uveitis

Control

p value

Central vascular density

11.60±4.17

12.63±4.40

0.531

Internal vascular density

19.97±3.50

22.64±2.12

0.023

Global vascular density

19.13±3.23

21.59±2.28

0.028

Studied parameters

Table 3 – Comparison of the macular vascular density in patients with Behçet uveitis and controls.

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Figure 1. OCT-A image of a patient with occlusive vasculitis 2 years ago

Table 4 – Correlation analysis between visual acuity or disease duration time. Studied parameters

Visual acuity (rho/ p value)

Disease duration time (rho /p value)

Central vascular density

0.445, p=0.110

-0.306, p=0.288

Internal vascular density

0.478, p=0.084

-0.212, p=0.466

Global vascular density

0.389, p=0.169

-0.256, p=0.378

Figure1. OCT-A image of a patient with occlusive vasculitis 2 years ago.Foveal Atrophy of the internal retinal layersp=0.129 is visible, corresponding avascular area -0.425, 0.108, p=0.712 to areas of absence of capillaries in the superficial and deep plexus’s in the OCT-A. Foveal avascular perimeter -0.444, p=0.113 0.000, p=1.000 Foveal circularity

0.370, p=0.193

0.020, p=0.945

Table 4 – Correlation analysis between visual acuity or disease duration time; and the quantitative parameters of area, perimeter and circularity of the foveal avascular zone as well as the parameters of macular vascular density.

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ORIGINAL ARTICLE » Silva D et al. OCT-A and Behçet

Figure 2. OCT-A image of a patient with occlusive vasculitis 2 years ago

Figure2. Example scan of the qualitative morphologic changes. The upper scans are from a patient with Behçet uveitis (previous diagnosis of panuveitis with vasculitis, currently resolved) where areas of capillary rarefaction on the superficial capillary plexus are observed (upper left) that are more accentuated in the deep capillary plexus (upper right). Below we can observe the scans from a control patient with the same age corresponding to the superficial capillary plexus (on the left) and deep capillary plexus (on the right) where these changes cannot be seen.

VISION PAN-AMERICA | JUL -SEP 2018 | VOL. 17 (3)

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ORIGINAL ARTICLE » Silva D et al. OCT-A and Behçet

Figure 3. Example scan of a patient with previous diagnosis of panuveitis without vasculitis, currently resolved.

Figure3. Example scan of a patient with previous diagnosis of panuveitis without vasculitis, currently resolved. The upper scans show the Behçet uveitis patient scans with superficial capillary plexus, deep capillary plexus and colorimetric analysis from left to right. Below are the corresponding scans of a control patient with the same age. Comparing the two patients, one can observe areas of capillary rarefaction on the superficial capillary plexus that are more accentuated in the deep capillary plexus. The colorimetric analysis, represents the superficial capillary plexus in red and the deep capillary plexus in green. One can observe qualitatively a greater reduction in the capillaries of the deep plexus compared to the superficial plexus. With this machine it is not possible to quantify changes in the deep capillary plexus.

Discussion OCT-A allows us to obtain high spatial resolution imagery of retinal circulation in a non-invasive way, and as such is being used as a method for studying retinal conditions, to identify vascular alterations not visible in fluorescein angiography, especially in the deep capillary plexus. Our study found vascular rarefaction in the superficial and deep capillary plexus in 8 eyes, 4 of which belong to patients without a previous diagnosis of retinal vasculitis by angiography. We also found statistically significant lower circularity index for these patients in comparison with the control group, as well as statistically significant alterations in internal and global vascular density in the superficial capillary plexus. Our findings suggest that Behçet uveitis patients might have microvascular alterations at the macular level in the absence of previously diagnosed retinal vasculitis. The clinical significance of VISION PAN-AMERICA | JUL -SEP 2018 | VOL. 17 (3)

these alterations is not evident, however. Our results agree with two previously published studies. Khairallah et al (2017) analyzed 44 eyes of 25 Behçet patients with ocular involvement in the posterior segment, comparing imaging findings obtained by fluorescein angiography, swept-source spectral domain OCT and OCT-A.19 Areas with perifoveal microvascular alterations such as disruption of the perifoveal capillary network, retinal capillary perfusion/non-perfusion areas and perifoveal capillary anomalies were more frequently observed by OCT-A than by fluorescein angiography (40.9 vs. 25%; p=0.039, 86.4 vs. 34.1%; p