Optik vetenskap 5 14

VETENSKAP # 5/2014 www.optikbranschen.se

Även yngre behöver undersökning av ögonen

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är detta skrivs är de blivande optikerna i full gång med sina examensarbeten. Det ska bli mycket spännande att läsa dessa och se vilka ämnen som tagits upp i år. Till er studenter på KI: Ta gärna kontakt så att även era arbeten kan publiceras här, det gäller både er på grundutbildning och magisterstudenter.

I detta nummer publiceras en magisteruppsats från KI. Den handlar om synskärpan efter VEGF behandling och om en ny korrektion efter behandling kan förbättra synskärpan ännu mer.

Det andra är en fallstudie från masterutbildningen vid Salus University, som handlar om Coat’s sjukdom.

Den visar på att förändringar i fundus inte bara är i de centrala delarna och att det inte heller bara är äldre personer som behöver en fullständig undersökning av ögonen. Även om det är vanligare att upptäcka AMD och glaucom som oftast uppkommer i högre åldrar så finns det betydligt fler sjukdomar som det ska finnas kunskap om när ögonbottenundersökningar utförs.

En del av dessa kan uppkomma även i yngre år och tänk på att ju yngre en person är, desto längre tid bör ögonen fungera framåt i tiden.

sjukdomar och förändringar har ökat betydligt. Det är inte alltid som synskärpan är påverkad i ett tidigt stadium av en förändring/sjukdom. Det innebär att om en fundusundersökning utförs först efter att synen är påverkad kan sjukdomen eller förändringen ha funnits länge och behandlingen inte blir lika effektiv. Samtidigt gäller det att veta vilka förändringar det är man ser, om det finns behandling eller om de ska följas upp.

Upplever du att kunskapen kunde vara större bör du passa på, sista ansökningsdatumet till kursen Diagnostisk Optometri är 1 juni. Om du inte har möjlighet att gå den är det ännu viktigare att regelbundet gå in på Optikerförbundets hemsida, där läggs även andra kurser ut.

Håll dig uppdaterad inom fortbildningsområdet och glöm inte att svara på frågorna som finns kopplade till denna tidnings artiklar, de hittar du på Optikerförbundets hemsida. Artiklarna i sin helhet finns på Optikbranschens hemsida. Ha en trevlig läsning och njut ordentligt av vårsolen.

Catarina Ericson

Ögonsjukvården har utvecklats mycket under de senaste åren och möjligheten till behandling av olika

n Artikel 1: Har patienter som behandlas med dyra anti-VEGF injektioner bästa möjliga korrektion?

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n Artikel 2: Coat’s sjukdom

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Catarina Ericson är OPTIK:s vetenskapsredaktör. Hon är MSc i Klinisk Optometri och Leg Optiker. e-post: catarina@c-optik.se

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Redaktörens kommentar:

I introduktionen ges en bra genomgång av vad VEGF är men också de olika undersökningarna som görs vid en sådan behandling. Resultatet är intressant, rätt korrektion spelar en viss roll.

Do patients wear optimal correction after expensive treatment with VEGF inhibitors?

AV ANNA-L ENA ÅBLAD och T H OM AS FRIS K M agisterpro grammet i klinisk o pto met ri 2012–20 1 3 KI

1. INTRODUCTION Age-related macular degeneration (AMD) is considered to be the leading cause of irreversible blindness among people in the developed world (Bressler, 2004; Resnikoff et al, 2004). Even though only 10% of all cases of macular degeneration are neovascular, they account for 90% of the visual loss leading to functional blindness (Chen et al, 2012).

The changes stimulating abnormal growth of new blood vessels under or within the macula are not fully understood, but vascular endothelial growth factor (VEGF) has proven to be one of the important factors in the formation of new blood vessels and the increase in vascular permeability (Adamis et al, 2006; Brown et al, 2006; Rosenfeld et al, 2006).

Knowledge about VEGF has changed the treatment for neovascular AMD. Ranibizumab (Lucentis; Novartis, Basel, Switzerland) is an antibody that binds to VEGF-A and inhibits neovascularization and reduces vascular permeability (Chen et al, 2012). Several studies show that this treatment is able to reduce visual loss and also has the potential to give an improvement in visual acuity (VA) (Brown et al, 2006; Rosenfeld et al, 2006; Regillio et al, 2008; Abraham et al, 2010; Krüger Falk et al, 2013). The results of these studies shows an increase in letters read both when administered monthly and when administered as needed.

Chen et al (2012) looked at the efficacy and safety of ranibizumab and they remarked that Optical coherence tomography (OCT) guided retreatment as needed may have the most optimal risk:benefit ratio due to less frequent injections. Most studies had a two year follow up, except Krüger Falk et al (2013) who evaluated a four-year treatment result. They noticed a decrease in VA after two to three years, but VA was maintained better in this group compared to patients treated with verteporfin in the ANCHOR-study (Brown et al, 2006).

In Denmark, a country with many similarities to Sweden the incidence of legal blindness caused by AMD in people aged 50 years or older decreased from 52.2 cases per

100 000 in the year 2000 to 25.7 cases per 100 000 in the year 2010 (Brandi Bloch et al, 2012). The bulk of reduction correlated well with the introduction of intravitreal VEGFinhibitor treatment in the year 2006.

Ranibizumab was approved for the treatment of neovascular agerelated AMD in June 2006 by the Food and Drug Administration (FDA), USA (http://www.centerwatch.com/drug-information/fda-approvals/drug-details. aspx?DrugID=904). While awaiting the approval of ranibizumab, ophthalmologists started using the off-label VEGF inhibitor bevacizumab (Avastin; Novartis, Basel, Switzerland), since the drug had similar target specificity as ranibizumab and a lower cost (Martin et al, 2012). Bevacizumab became the most commonly used drug in wet AMD treatment, even though it was not approved for treatment of neovascular AMD and there were no data from randomized trials supporting its use (Brechner et al, 2011). In the year 2008 bevacizumab accounted for 58% of all injections in the United States, but the cost for ranibizumab was 516 million dollars higher than the costs for bevacizumab (Brechner et al, 2011). To evaluate the intraocular safety and the duration of the therapeutic effect of bevacizumab compared to ranibizumab the CATT (Comparison of AgeRelated Macular Degeneration Treatment Trials) Research Group started a randomized trial (Martin et al 2011; Martin et al, 2012). They found similar effect on VA over a two-year period. The change in VA between baseline and follow-up was significantly higher with a monthly regimen compared to the regimen given as needed, based on VA and OCT, but ranibizumab and bevacizumab had similar effects when the dose regimen was the same (Martin et al, 2012). A higher rate of adverse events eas seen when using bevacizumab, but the data was considered uncertain because the conditions and side effects reported were not associated with inhibition of VEGF. One of the first symptoms in wet AMD is reading difficulties. Even so near vision has rarely been reported after treatment with VEGF inhibitors. Frennesson et al (2010)

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found that near VA improved significantly between baseline and a three months follow-up after ranibizumab treatment. Reading speed also increased significantly by 4347%, which also showed in improvement in quality of life, measured by Visual Function Questionnaire (VFQ-25). The improvement was larger when the better eye was treated, but were also seen when the worse eye was treated.

“Near” activities improved significantly compared to “distance” activities.

Many patients with low vision, for example those with large scotomas, report that glasses do not make them see better (Sunness et al, 2010). Distance correction therefore is not always taken into consideration and the patients only receive magnification aids for near vision without the benefit of a distance refraction.

Sunnes et al (2010) found that eleven percent of 739 patients with VA between 20/25 to no light perception had an improvement of VA of two lines or more on the ETDRS chart with new distance refraction. Median improvement was 2.8 lines, with a range from 2 to 10 lines.

It is most usual for patients, treated for neovascular AMD with intravitreal VEGF inhibitors, to be evaluated for treatment with OCT and best corrected visual acuity (BCVA). The patients’ visual acuity with their own spectacles is not taken into consideration. The treatment is expensive, especially when ranibizumab is the treatment of choice (Brechner et al, 2011).

Therefore the aim of this study was to find out whether these patients actually uses correction that gives the best visual quality by comparing BCVA values with habitual correction. A secondary aim was to study if optimal correction could lead to improved reading ability.

2. MATERIAL AND METHOD This study included 14 patients (9 females and 5 males), mean age was 75.7 years (SD=9.2). All patients had wet AMD and had received intravitreal injections at the Department of Ophthalmology, Vrinnevi Hospital in Norrköping, Sweden. They all received written information before entering the study and the patients who accepted signed an informed consent. The study was carried out according to the Declaration of Helsinki.

The trials took place during the patients’ regular follow up visits at the clinic. Patients receive three monthly injections initially after diagnosis. Follow up visits are planned every 6th week during treatment. Those visits include examination of BCVA with Early Treatment Diabetes Research Study (ETDRS) chart (Ferris et al, 1982) at 2 meters and with OCT (Topcon 3D OCT-1000).

Patients included in this study VA also underwent testing at 4 meters. Visual acuity was tested first with the patient’s own glasses, right eye with chart number 1 (see Appendix 3) and left eye with chart number 2. Binocular VA was tested with a Snellen chart at 5 meters.

Best Corrected Visual Acuity and best glass correction were obtained after trial frame refraction using the ETDRS R-chart at 4 meters. BCVA was tested with chart number 1 for the right eye and chart number two for the left eye. Bi-

nocular BCVA was tested with a Snellen chart at 5 meters.

All distance measurements were carried out in a dimmed room.

Near VA was tested with the patient’s own glasses and with the preferred addition of plus lenses to the distance refraction. Right and left eye was tested as well as binocular with Konstantin Moutakis near vision chart (Department of Ophthalmology, Lund University Hospital, Lund, Sweden). Near vision was graded in typographical points, the smallest test being 4 points and the largest 24 points.

Ordinary novel texts were used for the reading speed test, two different extracts from the same book. The two texts were used randomized to avoid any bias. Half the group read text A with their own glasses and text B after distance refraction with preferred plus lens addition for reading distance and vice versa.

All tests was performed with their own glasses first and then with best correction.

Statistics The statistical analysis was performed using the GraphPad Instat software and paired Student’s t-test was used for all measures. The level of statistical significance was set at P<0.05.

Subjects are presented as A-N, if both eyes were treated they are both presented in this table. If the patient’s best eye were treated it is marked with yes (Y). Visual acuity before refraction (Baseline) is measured by letters read on the ETDRS chart (4m) and near vision chart typographical points

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ded. With best correction and addition +3 dioptres the entire group improved near vision significantly to 5.2 (SD=1.8) points (p=0.029) (Figure 3). Near VA was also measured binocularly in 13 patients but the improvement (+13% p=0.054) was considered not quite significant.

Reading speed There was no significant differance in reading speed before and after our refraction of BCVA for the entire group of patients (N=12 p=0.87) (figure 4). Two patients (ID=F,J) were excluded due to low vision. Mean reading speed before refraction was 116 (SD=25) words/min for the entire group.

After refraction with BCVA the reading speed was almost the same, 117 (SD=27) words/min., i.e. , no significant difference was noticed.

Figure 1. ETDRS VA 4 m, before and after refraction.

The bars represents the subject´s mean visual acuity with habitual correction (Baseline) and best correction (BCVA). The lines indicate the standard devation.

Figure 2. Snellen VA 5m, before and after refraction.

The bars represents the subject´s mean visual acuity with habitual correction (Baseline) and best correction (BCVA). The lines indicate the standard devation.

3. RESULTS Visual acuity and reading speed of the entire group improved after refraction (BCVA). The improvement of Snellen, ETDRS and Near VA was significant for treated eyes.

Reading speed was measured in 12 patients. Regarding reading speed no significant differences were noticed (see Table 2).

ETDRS visual acuity The baseline VA (measured with habitual correction) for the entire group with treated eyes (N=18) was 64.1 (SD=13.6) letters on the ETDRS charts (4 m) before refraction. After refraction the BCVA increased to 68.6 (SD=11.0) letters and was considered very significant (p=0.008) (see Figure 1).

Snellen visual acuity Snellen visual acuity was messured binoculary (N=14) before and after refraction (5 m). The improvement of the entire group from 0.60 (SD=0.29) to 0.69 (SD=0.28) was very significant (p=0.006) (Figure 2). 7 patients gained >1 lines on the Snellen chart.

Near visual acuity The baseline mean near visual acuity for the group of treated eyes (N=16) was 6.5 (SD=2.3) points. One patient (ID=J) used only magnification glass for reading and was exclu-

4. DISCUSSION Several studies have shown a significant improvement in BCVA after treatment with VEGF inhibitors (Brown et al, 2006; Rosenfeld et al, 2006; Regillio et al, 2008; Abraham et al, 2010; Martin et al, 2012; Krüger Falk et al, 2013). These studies do not however take the patient’s own spectacles into consideration. Therefore the aim of the current study was to evaluate if the patient’s habitual correction gave visual acuity equal to their potential BCVA and when they differed to study the effect on reading ability.

We found a significant improvement in VA, both at distance and at near, in treated eyes. The improvement in ETDRS VA we found was nearly comparable to the MARINA study with gains of 6.5-11.3 letters after one year treatment (Brown et al, 2006). We saw a main improvement of 4.5 letters and a best gain of 18 letters with BCVA compared to habitual glasses. Binocular vision also improved significantly at distance. Binocular near vision improvement was not quite significant.

The qualities of near vision are rarely reported in other studies evaluating the benefits of intravitreal VEGF-inhibitor treatment. Frennesson et al (2010) found a significant improvement of near vision acuity and reading speed after 3 months treatment. Even BCVA measured with ETDRS did improve, but they found no correlation between improvement in BCVA and near vision.

Källmark et al (2010) did see a significant improvement in distance visual acuity but no significant difference in reading speed. There was a significant difference in comprehension of the text though. Near visual acuity was not tested. Frennesson et al (2010) used regular novel texts, two extracts from the same book and the patients read for three minutes. Those who read 4-10 points on the near vision chart used +4 dioptres addition, near vision 12 points used +5 dioptres addition and so on up to +10 dioptres addition for 24 points in near vision. Källmark et al (2011) used two newspaper texts on a Tobii eye tracker and the patients read from the screen at 60 cm distance. The text was presented in a 24 points font over six pages. Maybe the different ways of testing reading speed makes a difference.

The reading speed on average of our patients did not improve with best correction either, even though the way of

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fect of the treatment and is a small cost in the context. In Sweden the ophthalmology clinics do not have the resources to do careful examinations of refractive errors and fitting of low vision aid or optimal correction. Instead patients should be recommended to see an optometrist after treatment to make the most of it, both considering visual acuity for the patients and cost efficacy for the healthcare system.

CONCLUSION This pilot study show that few patients wear optimal correction after treatment of wet AMD. Considering the significant costs associated with the intravitreal injections given to these patients it seems relevant to ensure that patients use optimal correction to fully benefit the positive effects of the treatment. n Figure 3. Near vision, before and after refraction, points The bars represents the subject´s mean visual acuity with habitual correction (Baseline) and best correction (BCVA). The lines indicate the standard devation.

Fewer points means better vision acuity.

Figure 4. Reading speed, before and after refraction, words/min The bars represents the subject´s mean visual acuity with habitual correction (Baseline) and best correction (BCVA). The lines indicate the standard devation.

testing was more similar with Frennesson et al (2010). Perhaps fatigue made a difference since the patients’ reading with best correction took place at the end of our examination, after 30-40 minutes? All together the results from studies evaluating reading ability show how difficult it is to find a sensitive and adequate test to measure this particular function.

Our study does not include enough patients to give a certain result, but with the patients included we did see a significantly better VA with our refraction compared to their own habitual correction. Even if the improvement was of less significance binocular than monocular, it might be of importance to the patients anyhow. Frennesson et al (2010) saw a significant improvement in quality of life on near related tasks even though the worst eye was treated.

The treatment with VEGF inhibitors is a costly treatment, both considering the drugs and personnel costs. When we looked retrospectively in the patients’ case notes there were a stable refraction between different visits at the clinic, with the possible exception of those occasions when a new injection was needed. The results from this study show the importance of BVCA and refraction of the patients after intravitreal VEGF-inhibitor treatment. It would be interesting to make a new study with a bigger material to see if the results would be the same. We do however think that new spectacles for the patients could assure best ef-

REFERENCES Abraham P, Yue H, Wilson L. Randomized, Double-Masked, Sham-Controlled Trial of Ranibizumab for Neovascular Age-Related Macular Degeneration: PIER Study Year 2.

Am J Ophthalmol 2010;150:315-324.

Adamis AP, Shima DT. The Role of Vascular Endothelial Growth Factor in Ocular Health and Disease. Retina 2005;25:111-118.

Brandi Bloch S, Larsen M, Munch IC. Incidence of Legal Blindness From Age-Related Macular Degeneration in Denmark: Year 2000 to 2010. Am J Ophthalmol 2012;153:209-213.

Brechner RJ, Rosenfeld PJ, Babish JD, Caplan S. Pharmacotherapy for Neovascular Age-Related Macular Degeneration: An Analysis of the 100% 2008 Medicare Fee-For-Service Part B Claims File. Am J Ophthlmol 2011;151:887-895.

Bressler NM. Age-Related Macular Degeneration is the Leading Cause of Blindness. JAMA 2004;291:1900-1901.

Brown DM, Kaiser PK, Michels M, et al. Ranibizumab versus Verteporfin for Neovascular Age-Related Macular Degeneration. N Engl J Med 2006;355:1432-1444.

Brown DM, Michels M, Kaiser PK, et al. Ranibizumab versus Verteporfin Photodynamic Therapy for Neovascular Age-Related Macular Degeneration: To-Year Results of the ANCHOR Study. Ophthalmology 2009;116:57-65.

Chen Y, Han F. Profile of Ranibizumab: Efficacy and Safety for the Treatment of Wet Age-Related Macular Degeneration. Therapeutics and Clinical Risk Management 2012;8:343-351.

Ferris FL 3rd, Kassoff A, Bresnick GH, Bailey I: New Visual Acuity Charts for Clinical Research. Am J Ophthalmol 1982;94:91-96. Optimal correction after VEGF inhibitors?

A-L Åblad and T Frisk Frennesson C, Nilsson UL, Peebo BB, Nilsson SEG. Significant Improvements in Near Vision, Reading Speed, Central Visuual Field and Related Quality of Life After Ranibizumab Treatment of Wet Age-Related Macular Degeneration. Acta Ophthalmica 2010;88:420-425.

Krüger Falk M, Kemp H, Lykke Sørensen T, Four-Year Treatment Results of Neovascular Age-Related Macular Degeneration With Ranibizumab and Causes for Discon-

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tinuation of Treatment. Am J Ophthalmol 2013;155:89-95 Källmark FP, Kvanta A, Öqvist G, Brautaset R. Increased Visual Acuity Will Not Necessarily Equal an Increased Reading Ability in Patients with Subfoveal Neovascular Macular Degeneration. International Journal of Clinical Medicine 2011;2:404-410.

Martin DF, Maguire MG, Fine SL, et al. Ranibizumab and Bevacizumab for Treatment of Neovascular Age-related Macular Degeneration: Two-Year Results. Ophthalmology 2012;119:1388-1398.

Martin DF, Maguire MG, Ying GS, et al. Ranibizumab and Bevacizumab for Neovascular Age-related Macular Degeneration. N Engl J Med 2011;364:189-1908.

Regillo CD, Brown DM, Abraham P, et al. Randomized, Double-Masked, Sham-Controlled Trial of Ranibizumab for Neovascular Age-Related Macular Degeneration: PIER Study Year 1. Am J Ophthalmol 2008;145:239-248.

Resnikoff S, Pascolini D, Etya’ale D, et al. Global Data on Visual Impairment in the Year 2002. Bull World Health Organ 2004;82:844-851.

Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for Neovascular Age-Related Macular Degeneration. N Engl J Med 2006;355:1419-1431.

Sunness JS, El Annan J. Improvement of Visual Acuity

by Refraction in a Low-Vision Population. Ophthalmology 2010;117:1442-1446.

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Redaktörens kommentar:

Här är det intressant med hela följden av undersökningar från upptäckt till olika försök med behandling. Det är bra bilder som visar förloppet och i diskussionen kommer ännu mer fakta fram.

Coat’s disease AV JEANETTE BRANDT MSc i Klinisk Optometri, Leg Optiker .

INFORMATION ABOUT THE PATIENT

Initials Age Gender Rase Occupation Date of exam

MS 15 Female Caucasian Student May 11, 2010

HISTORY MS, a 15 year old female, arrived in the clinic for an eyeexamination because she thought that her vision with her left eye had decreased. She had also noticed a blurry spot in her central vision field in that eye.

Her parents had also noticed that her left pupil looked a little yellow in pictures.

All this was noticed the latest three or four weeks.

MS had her last eye examination in February 17, 2010 with a VA (Visual Acuity) of 20/20 in both eyes and her eyes then looked healthy.

MS has been wearing glasses since she was ten years old.

Her latest glasses were since February 2010.

In that time she also started with daily disposable contact lenses. She wears them occasionally.

She did not have any other specific problems, and had not experienced any pain, grittiness, itching or burning in her eyes. She thought she had a good vision with her right eye.

She reported neither diplopia nor headache.

The patient had never had any infections, injuries or surgery to her eyes.

She has never been referred to an ophthalmologist.

Her grandmother had been diagnosed for cataract, but apart from that there were no history of eye disease in her family. Neither could she recall that there were any systemic diseases in her family.

She was healthy and had no medications or allergies.

She was not a premature child.

She did not smoke, neither did she used alcohol or drugs.

Her last physical exam was in school, September 2009.

Objective findings At the examination she wore her glasses since February 17, 2010. At that time her corrected VA (visual acuity) in RE (right eye) and LE (left eye) was 20/20.

Table 1 and 2 show VA, Refraction and Initial procedures.

The initial procedures were all performed with her current prescription, apart from confrontation fields and motility, which was performed unaided.

Anterior segment examination Lids and lashes appeared clean and healthy in slit lamp examination and there were no blepharitis. Bulbar and palpebral conjunctivae were also quiet in both eyes. Both corneae were clear with a healthy-looking endothelium and the corneae were about 12,0 cm in diameter.

Anterior chambers were clear without any cells and flares. The anterior chamber angles were open, and graded by van Herrick´s method to grade 4 nasally and temporally.

Both irides were green, with no nodules or transillumination.

With an all-over view there was a slight yellowish reflex from macula through the pupil in LE. Keratometry readings RE 7,64 / 7,84 x 173° LE 7,56 / 7,77 x 14°

K-cylinder -1,127 x 173° K-cylinder -1,207 x 14°

Posterior segment examination Fundus examination was performed without dilation of the pupil.

It was made with SL ophthalmoscopy and a fundus photo was also taken (Figure 1). It was taken with TopCon TRC – NW200 (a non mydriatic retinal camera) RE showed a healthy, evenly pigmented fundus with an optic nerve head that looked pink, healthy and distinct.

The cup/disc ratio was estimated to 0,3 /0,3.

Her macula was normal, flat and dry and macula reflex was present.

The A/V ratio was 2/3 and no HR or AS. LE showed an optic nerve head that was pink, healthy and distinct.

The cup/disc ratio was estimated to 0.3/0.3.

Her macula looked quite normal in the centre, but the

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TABLE 1. VAS AND REFRACTION Her current spectacle Rx RE sf -1,75 cyl -0,25 ax 175°

LE sf +0,25 cyl -1,0 ax 25°

UnCorrected VA (UCVA) RE

LE 20/100

Bino 20/100

VA 20/20 VA 20/100 Bino 20/20

20/200

New Rx RE Rx sf -1,75 cyl -0,25 ax 175°

LE Rx sf -0,25 cyl -1,0 ax 25°

VA 20/20 VA 20/100 PHNI VA 20/20

TABLE 2. INITIAL PROCEDURES Cover test

Dist: Near:

ortophoria 2 exophoria

NPC

4 cm

Amplitude of accommodation

RE: LE: Bino:

Stereopsis, Titmus Fly Stereotest

No stereopsis

Ocular motility

Full and smooth in all directions, no pain or diplopia

Pupils

3/6 +4 Both pupils were round and the same size. Pupils equally PERRLA reactive to light and accommodation. RAPD-3/6 +4

Confrontation fields

RE: LE:

Full by PFC, CFC, HC and SPC Full by PFC, CFC, SPC. HC showed hand to the right darker

Color vision (Ishihara)

RE: LE:

15/15 12/15

10D could not be measured 10D

colour of the macula was “a little dark”. Macula reflex could not be seen. There were exudates temporally and inferiorly of the macula.

In the posterior pole there were exudates. Near the macula, there were exudates in a circinate pattern, mainly temporally, reaching out in the peripheral parts with more exudates.

The A/V ratio was 2/3 and no HR or AS.

Other relevant examinations Intraocular pressure was performed using a non-contact tonometer (Topcon CT-80) at 6 pm, and found to be 12,0 mmHg in RE and 11,0 mmHg in LE. When she looked at the Amsler grid she saw the lines correct with her RE, but with her LE she said that it was blurry in the middle and that some lines, both horizontally and vertically, looked wavy.

Assessment A1: Myopia in both eyes, with an astigmatism LE A2: Decreased VA and a positive Amsler test LE A3: Exudates in retina LE, concentrated temporally Plan / Management P1: Her latest glasses / prescription was the same as the new refraction, so no new spectacles

FIGURE 1.

Figure 1a shows fundus RE. Figure 1b shows fundus LE

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P2/P3: Referral to ophthalmologist for fundus examination and diagnosis of the findings Report from the Ophthalmologist MS was first sent to the Ophthalmologist at the Eye-clinic of the local hospital in Värnamo. (there was no referral letter, we phoned the eye-clinic the next day and made an appointment) She was there in May 12, 2010.

There they took notice about the decreased VA, and the exudates in her fundus LE. They sent over a letter of referral to the Eye Clinic Ryhov, County hospital in Jönköping, and there she was in May 19, 2010.

They got a UCVA of 20/50 in LE. A Fluoroangiography was made and showed vessel anomalies in retina with partially teleangiectasic vessels and some areas of leakage temporally.

They suspected Coat´s disease, so they sent her to a retina specialist.

(Appendix 1) So in June 22, 2010 the patient went to an Ophthalmologist at the University Hospital in Linköping.

They examined both her eyes.

RE: Anterior and posterior segment were fine. Nothing suspected.

LE: Anterior segment normal, no irisrubeosis.

She was dilated: the lens and vitreous was clear. The papilla was normal.

Fundus: Hard exudates temporally, a little bit peripheral and subfoveal, more central.

They noticed that the exudates had become more since her visit at the first Opthalmologist.

They also noticed changes in bloodvessels and microaneurysms, this was in the periphery. The bloodvessels there had different thicknesses. There was also a slight elevation of retina in the periphery.

An OCT was made. There they saw a thickness in fovea with inserted exudates.

They made the diagnosis: Coat´s disease.

The patient was informed about it and she had a laser treatment directly.

Then she was scheduled for a next visit in a couple of months.

(Appendix 2) Advice given to the patient • The patient was educated to be aware of changes in her healthy right eye, although Coat´s disease is always (almost) unilateral.

• The patient was told to be aware of changes in her LE, such as floaters, flashes or visual field defects.

• The patient was educated to use protective eye wear in situations that demand extra care towards eye injuries.

• The patient was educated only to use her daily disposable contact lens on her healthy eye only if necessary, due to the risk to get an infection.

Follow up at the Ophthalmologist and in our clinic After her first laser treatment in June 22, 2010 at the University Hospital in Linköping, she had several appointments there for examination and treatment.

August 24, 2010 Linköping, University hospital She said that she saw a little better after her first laser treatment in June.

But now she had noticed curved lines and flashes now and then.

LE UCVA 20/200 There were more exudates now.

She had another laser treatment.

September 25, 2010 – fundus photo was taken in our clinic LE (Figure 2) October 19, 2010 Linköping, University hospital UCVA: FC 50 cm More changes in bloodvessels now.

A new laser treatment was made.

January 18, 2011 Linköping, University hospital UCVA: FC 1 m Microaneurysms and changes in bloodvessels in the periphery: temporal and inferior.

A laser treatment was made to the inferior changes.

January 27, 2011 – fundus photo was taken in our clinic LE (Figure 3) April 6, 2011 Linköping, University hospital UCVA 20/200 in 3 m Hard exudates and a vesicle in the macula and changes in blood vessels temporally. She had another laser treatment.

April 21, 2011 – fundus photo was taken in our clinic LE (Figure 4) Then she had one visit in Linköping, May 2011: nothing was done.

June 14, 2011 Linköping, University hospital UCVA FC 1m, excentric fixation Retina was swollen with subretinal changing that lifts temporal part of macula.

They also saw microaneurysms, dilated bloodvessels in temporal periphery.

They now discussed an Avastininjection. (Avastin, with Bevacizumab, which is an anti-VEGF, which is often given to patients with metastatic cancer, breastcancer the most common 7).

FIGURE 2 – fundus photo LE, September 25, 2010

FIGURE 3 – fundus photo LE, January 27, 2011

FIGURE 4 – fundus photo LE, April 21, 2011

10 OPTIK VETENSKAP # 5-2014 n August 10, 2011 Linköping, University hospital MS had an intravitreal Avastininjection in her LE August 19, 2011 – fundus photo was taken in our clinic LE (Figure 5)

FIGURE 5 – fundus photo LE, August 19, 2011

FIGURE 6 – fundus photo, October 13, 2011

FIGURE 7 – fundus photo LE, April 3, 2012

September 15, 2011 Linköping, University hospital UCVA 20/200 in 1 m.

Her Left eye looked the same as before the Avastininjection.

She was now planned for a Cryo treatment in anaesthesia.

October 13, 2011 – fundus photo was taken in our clinic LE (Figure 6) MS had her Cryo treatment in November 4, 2011, at Linköping, University hospital.

She got Maxidex x 3-4 and cyclogyl x 2 to continue with until the next checkup, in about 2-3 weeks.

(MAXIDEX is a type of cortisone and belongs to the group of medicines called corticosteroids. It is used to treat the redness, swelling and other symptoms of eye inflammation 7) November 23, 2011: She was now back in Eye Clinic Ryhov, County hospital in Jönköping They saw a big lipid infiltrate in macula. Retina was adjacent.

There were pigmentations in the peripheral retina from laser and Cryo treatment.

They told her to stop with cyclogyl but continue with Maxidex for a couple of weeks, but just x 1.

December 21, 2011 Ryhov, County hospital, Jönköping UCVA <20/200 There was a big “cake of exudates” in macula and retinal edema, but no vascular changings or no vitreous hemorrhages.

January 19, 2012 Ryhov, County hospital, Jönköping UCVA <20/200

She now had a slight conjunctival injection with a low amount of cells and flares in anterior chamber.

She also had some isolated cells in vitreous. Exudates in macula as before and some retinal edema. Also peripheral exudates.

Since there were signs of inflammation they gave her Maxidex again.

March 9, 2012 Ryhov, County hospital, Jönköping UCVA <20/200 Almost the same as last visit: but now a clear vitreous, and the peripheral exudates had decreased. A streak of fibrosis between the papilla and the area of exudates in macula.

There were calibre changes of retinal vessels but it was not proliferative. Retina was adjacent.

They told here to continue with Maxidex for another month and she was then scheduled for her next visit in three months.

April 3, 2012 – fundus photo was taken in our clinic LE (Figure 7) June 04, 2012 MS had a visit at our clinic directly after being at the Eye Clinic Ryhov, County hospital, Jönköping.

MS said that they told her that everything looked fine. She will be back in about 3 months.

IOP 10 mmHg, both eyes.

Fundus photos was taken in our clinic RE and LE (Figure 8) DISCUSSION Coat´s Disease or Retinal Teleangiectasia Coats’ disease was first identified by the Scottish ophthalmologist George Coats in 1908.

Coats’ disease is also known as Coats’ Retinitis, Coats’ Syndrome, Exudative Retinitis and Retinal Telangiectasis.

The word telangiectasias or angioectasias are small dilated blood vessels near the surface of the skin or mucous membranes, measuring between 0,5 to 1,0 mm in diameter.

Here there are retinal telangiectasis, leading to leakage with intraretinal and subretinal exudations and frequently exudative retinal detachment.

Patients with Coat´s disease have abnormalities of the vascular endothelium, which becomes permeable 5.

Presentation Coat´s Disease is an idiopathic, non-hereditary disease 1.

The condition is very rare.

FIGURE 8 – fundus photos June 04, 2012. 8a RE, 8b posterior pole LE, 8c the temporal periphery LE

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It is a non familial development, though the telangiectasia is congenital.

75% are males and the vast majority (about 90%) has involvement of only one eye.

They show up with visual loss, strabismus or leucoria1.

Coat´s disease mostly presents in the first decade of life, at an average age of 5 years. These are the more severe cases 1.

It can present in later childhood but rarely in adult life.

There have been cases of onset up to 71 years 8.

There are no systemic disease associations.

There is some evidence to suggest that Coats’ Disease is caused by a somatic mutation of the NDP gene. (Norrie Disease Protein)4.

are thought to originate from retinal histocytes, retinal pigment epithelial cells, or lipidladen macrophages3.

Clinical picture There are retinal telangiectasias, which are small dilated blood vessels. These retinal vascular abnormalities result in small multifocal outpounchings/aneurysms of the retinal vessels, leading to leakage with intraretinal and subretinal exudate formations1. In the beginning you see yellow intra/ subretinal exudation that form circinate pattern at vessels 5.

Then frequently it may lead to exudative retinal detachment.

The exudates (extensive yellow intraretinal and subretinal exudates) or the retinal detachment gives the leucoria.

Signs There are several signs in Coat´s disease, and one of them is leucoria, which is a white pupilreflex. Leucoria may develop secondary to an exudative retinal detachment or to extensive yellow intraretinal and subretinal exudates.

Then there are these teleangiectasis in the retina. They are most often in the inferior and temporal quadrants between the equator and ora serrata.

Sometimes the lesions are located posterior to the equator towards the vascular arcades.

Progression of intraretinal and subretinal yellowish exudations often affecting areas remote from the vascular abnormalities, particularly in the macula.

The end result of Coat´s disease, if it is allowed to progress unchecked, is retinal detachment.

Flourescein Angiography can in mild cases show early hyperflourescence of the teleangiectasis and late staining and leakage 1.

What happens then in Coat´s disease?

There are localized areas of retinal teleangiectasias with localized areas of exudation and retinal hemorrhage.

The small dilated bloodvessels are at the level of inner nuclear and inner plexiform layer of the retina.

These can be “mild”, but then there can be larger areas of the retinal teleangiectasis with larger hemorrhages, massive exudation, retinal edema and exudative retinal detachment.

The progression may result in rubeosis, retinal and/or vitreal hemorrhage, secondary glaucoma and eventual enucleation.

So during the follow-up it is important to check IOP frequently.

The breakdown in the blood-retinal barrier results in the development of cystic cavities filled with proteinacious fluid and the accumulation of lipid-rich fluid within and underneath the retina.

The macrophages pick up the lipids and migrate, resulting in intraretinal and subretinal exudation.

In addition to exudation that causes vision loss, the intraretinal edema may spread to the posterior pole, creating cystoid macular edema.

Ischemic foci may develop within the capillary bed near the teleangictasia.

Retinal hemorrhage, neovascularization, and subsequent vitreous hemorrhage may occur in these areas of hypoxia.

As the exudative process evolves and becomes more chronic, cholesterol crystals accumulate, and tortuous vessels develop in the periphery with the potential for arteriovenous shunting.

Ghost cells characteristic of Coat´s disease appear and

There are five stages of Coat´s disease3: Stage 1 - retinal vessel teleangiectasia (dilated tortuosity, edema, minor exudates) Stage 2 - localized intraretinal exudates (obscuration of teleangectasia by exudate) Stage 3 - localized (partial) retinal detachment (sensory RD by subsensory exudate) Stage 4 - total retinal detachment (massive exudation and subretinal membrane) Stage 5 - uveitis, phthisis bulbi, glaucoma, cataract, massive subretinal membrane

Complications There are several complications to Coat´s disease. Rubeosis iridis, glaucoma and uveitis are a few.

In painful eyes with neovascular glaucoma, enucleation can be necessary.

Cataract may also be a complication.

At the posterior segments, massive subretinal membrane and central serous macular edema may present. Retinal and vitreal hemorrhage can occur and also neovascularisation.

At a later stage, phthisis bulbi, which is a shrunken nonfunctional eye, may occur1.

Treatment1 Just observation in patients with mild, non-vision threatening disease (i.e. just mild dilation of vessels with no edema or exudates 3) and in those with a comfortable eye with total retinal detachment in which there is no hope of restoring useful vision.

Laser photocoagulation to areas of telengiectasis, if there is progressive exudation. This you do in stage 1 to 4.

Often more than one treatment session is required to obliterate the peripheral teleangiectasias and to reduce the exudation in the macula.

The best candidates for photocoagulation include patients

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with central visual loss caused by exudation from focal extramacular teleangiectasia and children, because of the poorer prognosis when the disease presents at an earlier age.

Photocoagulation is most effective in eyes without retinal detachment1.

Then you do Cryotherapy in eyes with extensive exudation or subtotal retinal detachment. This may result in marked reaction with increased leakage. Therefore, the photocoagulation is the preferred option if possible.

The Cryotherapy might be done in stage 1 to 4.

In stage 3 also a drainage of subretinal exudates might be done.

Also Vitreoretinal surgery may be considered, especially in eyes with total retinal detachments and a poor visual prognosis. A successful retinal re-attachment often prevents the subsequent development of neovascular glaucoma.

Then in total retinal detachment there is scleral buckle 3.

In stage 4 they do this, often in combination to photocoagulation and cryotherapy.

You also give symptomatic relief of pain in uveitis, phithisis bulbi, glaucoma, cataract and massive sub-retinal membrane. This is in stage 5. In painful eyes with neovascular glaucoma enucleation may be the only way to go.

Prognosis: The prognosis is variable and dependent on the severity of involvement at presentation.

The end result of Coat´s disease, if it is allowed to progress unchecked, is retinal detachment3.

Young children, particularly those under 3 years of age, often have a more aggressive clinical course and often already have extensive retinal detachment at presentation1.

The earlier the disease is detected and the earlier the application of therapy, the better the diagnosis3.

However, older children and young adults have a more benign disease with less likelihood of progressive exudation and retinal detachment, and in some cases spontaneous regression may occur1.

Differentialdiagnosis1 Differentialdiagnosis to Coat´s disease includes other causes of unilateral leucoria and retinal detachment in children: Retinoblastoma is one of them. It is a malignant tumour, but seldom seen after 3 years of age. That is because Retinoblastoma results from malignant transformation of primitive retinal cells before final differentiation. It may be heritable or non-heritable.

Then Toxocariasis is another diffrentialdiagnosis. It is caused by a common intestinal ascarid (roundworm) of dogs called Toxocara canis.

It presents at the ages between 2 and 9 years old with leucoria, strabismus or unilateral vision loss.

Signs can be anterior uveitis and vitritis, peripheral granuloma or a dense greyish-white exudate that covers the peripheral retina and pars plana, similar to “snowbanking” seen in pars planitis

Incontinentia pigmenti ( Bloch-Sulzberger syndrome), a rare X-linked dominant disorder that is affecting girls.

About one-third of the children develop cicatricial retinal detachment in the first year of life which may cause Leocoria.

Concerning Leber miliary aneurysms, it is now considered that Coat´s disease and Leber miliary aneurysms represent a spectrum of the same disease.

Leber miliary aneurysms is more localized and carries a better visual prognosis.

Other differentialdiagnosis are Neovascularization after BRVO, Familial Exudative vitreoretinopathy, and Idiopathic Juxtafoveal Retinal Teleangiectasia 2.

Then there are several differentialdiagnosis to Leucoria 1: Persistent hyperplastic primary vitreous, but often associated with a small eye and cataract present at birth or early in life Congenital cataract Retinal astrocytoma, a rare and benign tumor of the retina, but associated with giant drusen of the optic disc Retinopathy of prematurity Myelinated nerve fibers Uveitis Retinochoroidal coloboma, a congenital abnormality caused by faulty of closure of the embryonic fissue, light areas of nonpigment is seen Capillary hemangioma, 50% bilateral, distinct red tumor often at skin, but also in eye, congenital Cavernous hemangioma, a benign tumor that is found to grow within the orbit, proptosis, no exudation, rare hemorrhages Retinoblastoma, described above DISCUSSION OF FINDINGS At MS visit at May 11, 2010 she told us that her family had noticed a yellowish/white pupil at photos taken of her lately.

She also told us that she had a blurry spot in her central visual field of her left eye.

That made a few differential diagnoses coming up. But most of the diagnoses with leucoria present at birth or early in life, i.e. the first years after birth.

There were no bulging or protrusion at retina so no there was no suspect of tumour or any blastoma. Also the optic disc, lens, vitreous and anterior segment were clear and normal. The IOP was 12 mmHg in RE and 11 mmHg in LE, so that was nothing suspected as well1.

But then the examination of the posterior segment along with the fundus photo, gave us the typical clinical picture of Coat´s disease. Her fundus photo was almost exactly how they show Coat´s disease in several books 1, with exudates that form a circinate pattern at vessels.

The findings at her visit were typical for Coat´s disease, the only not typical was gender and age. MS was a girl at 15 years old and the typical candidate for Coat´s disease is a boy at 5 years old 5.

MS was a young healthy female and there were no history of illness and eyedisorders and not in her family either, despite from her grandmother having cataract. As Coat´s di-

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sease is an idiopathic, non-hereditary condition, though the telangiactasia is congenital, she just had the bad luck to get it.

Coat´s disease is listed as a “rare disease” by the ORD9.

A rare disease occurs in less than 200 000 individuals in the United States, or less than 5 per 10 000 individuals in the European Union. In Sweden it is rare if it affects less than 100 in 1000 000 10. A figure that was mentioned at the University hospital in Linköping where MS had her treatments was that Coat´s disease affects approximately 3-4 Swedes every year, usually small boys.

At her last examination in February 17, 2010 her corrected VA was 20/20 in both eyes and her fundus photo and the posterior segment examination showed nothing extra ordinary. Then when this examination takes place, less than three months afterwards, the clinical picture looks a lot different. If an OCT had been made in February 17, 2010, it might have shown something, but since nothing then was suspected and she then only came for new glasses, she was not referred to that kind of examination.

But the fact that the diagnosis was made at a relative early stage at Coat´s disease and that therapy was set in early makes the prognosis better for the left eye of MS 3. It is a fact that the earlier the disease is detected and the earlier the application of therapy, the better the diagnosis. Older children and young adults have a more benign disease with less likelihood of progressive exudation and retinal detachment, and in some cases spontaneous regression may occur.

Young children, particularly those under 3 years of age, often have a more aggressive clinical course and often already have extensive retinal detachment at presentation.

Several therapies were set in and from June 22, 2010 until November 4, 2011 she had five laser treatments, one Avastininjection and one Cryotherapy.

The Avastin, with Bevacizumab, which is an anti-VEGF, is often given to patients with metastatic cancer (breastcancer the most common) 7. In Coats’ disease, it is believed that Avastin would greatly inhibit the development of new blood vessels.

The photocoagulation with focal laser is done to burn leaking bloodvessels and to prevent new ones to come. That also made the edema decrease.

The goal of cryotherapy, the local use of low temperature, which MS had, is to decrease cellular metabolism, increase cellular survival, decrease inflammation, decrease pain and spasm and to promote vasoconstriction. Then I had a discussion with an ophthalmologist11 at the eye-clinic in Värnamo, who had thoughts about another treatment for MS. It is about using stem-cells from the retinal pigment epithelium. Stem-cells are “immature cells” which can function as spare-cells when the retina “needs to be repaired”. A lot of research is going on about stem-cells, about learning how these cells lives and how to stimulate them to be able to do the “reparation”12. Hopefully this method can be used to my patient.

At her latest visit to the ophthalmologist in June 4, 2012 they were satisfied with her fundus and nothing was done.

She will return in about 3 months. She will go on with her

spectacles and only use her daily disposable contact lenses in her RE if it is necessary, due to the risk of an infection.

Hopefully there will be no retinal detachment, neovascular glaucoma or uveitis and that would be a good prognosis for her disease. The fact that Coat´s disease is a unilateral condition is also a relief for the patient.

MS will have a lot of visits at the ophthalmologist during the years so her disease will be good taken care of.

Commonly patients with Coat´s disease will be followed up quarterly if vision remains normal3.

The importance of following up frequently is of course due to her Coat´s disease in her left eye, but it is also to have her right, healthy eye under control. Fortunately Coat´s disease is almost always unilateral, figures says unilateral in 90% of the cases 1.

CONCLUSION When MS, a 15 year old female, got her latest spectacles in February 2010, her eyes showed no signs of any diseases and her visual acuity was 20/20 in both eyes. Then within 3 months, in May 2010 this clinical picture of Coat´s disease showed up. The diagnosis Coat´s disease was determined by the ophthalmologist and the application of therapy could start in an early stage of the disease.

Also the fact that she was 15 years old at presentation made the prognosis better.

It has been found that older children and young adults have a more benign disease with a smaller risk of progressive exudation and retinal detachment and there have also been cases with spontaneous regression.

MS was not the typical candidate for Coat´s disease, seen to age and gender. 75% of the patients are males and the diagnosis mostly presents at the first decade of life.

MS was educated about her condition and there will be a time with regularly check-ups at the ophthalmologist and probably more therapy. She will also be followed up at our clinic. MS was told to be ware of flashes, floaters or anything else coming up to her eyes and vision. She was also told about the importance of protecting her healthy eye. n

REFERENCES: 1. Jack J Kanski, Clinical Ophthalmology, a system approach, Sixth edition, Butterworth Heinermann Elsevier 2. The Wills Eye Manual, Office and Emergency room, Diagnosis and treatment of Eye Disease, Justis P.Ehlers and Chirag P.Shah 3. Larry J. Alexander, Primary Care of the Posterior segment, Third Edition 4. Coat´s disease: information for patient, www.coatsdisease.org, Dr. Shields, Wills hospital was one of the informer to this website 5. Lynn Hong Trieu, OD, MS , Pennsylvania College of Optometry at Salus University 6. Beatrice, Bourghardt Peebo, Ophthalmologist at eye-clinic Ryhov hospital, Jönköping, Sweden 7. www.FASS.se, The Swedish Pharmacopeia Drug Information, 8. Website: www.coatsdiseasefoundation.org. The Jack McGovern Coat´s disease foundation 9. Office of Rare Diseases (ORD) of the National Institute of Health (NIH).

10. Rare diseases Sweden. www.sallsyntadiagnoser.se 11. Khaled El-Naggar, Chief Ophthalmologist at Eye Clinic in Värnamo, Sweden 12. http://skane.se/sv/Webbplatser/SUS/Skanes-universitetssjukhus-Lund/