Dose: 75-100 mg / dieRazionale

Effetto antiaggregante che contrasta:

aumento fattori procoagulanti nella CRSCaumento aggregazione piastrinica indotto dagli steroidi

Riduce il rilascio di cortisolo e cate-colamine in risposta allo stress (Caccavale et al.

Clin Ophthalmol 2011)

ASPIRINA

ASPIRINA

© 2011 Caccavale et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.

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DOI: 10.2147/OPTH.S17182

Central serous chorioretinopathy: a pathogenetic model

Antonio Caccavale1 Filippo Romanazzi1 Manuela Imparato1 Angelo Negri2 Anna Morano3 Fabio Ferentini2

1Department of Ophthalmology, Neuropthalmology and Ocular Immunology Service, 2Department of Ophthalmology, Hospital “C. Cantù”, Abbiategrasso, Milan, Italy; 3University Eye Clinic, Foundation IRCCS San Matteo Hospital, Pavia, Italy

Correspondence: Antonio Caccavale Hospital “C. Cantù” Abbiategrasso, 20081 Milan, Italy Tel 39 029486202 Fax 39 029486202 Email neureye@katamail.com

Abstract: Despite numerous studies describing predominantly its demography and clinical course, many aspects of central serous chorioretinopathy (CSCR) remain unclear. Perhaps the major impediment to finding an effective therapy is the difficulty of performing studies with large enough cohorts, which has meant that clinicians have focused more on therapy than on a deeper understanding of the pathogenesis of the disease. Hypotheses on the pathogenesis of CSCR have ranged from a basic alteration in the choroid to an involvement of the retinal pigment epithelium (RPE). Starting from evidence that affected subjects often present a personality prone to stress with altered pituitary–hypothalamic axis response (HPA) and that they have higher levels of serum and urinary cortisol and catecholamines than healthy subjects, we hypothesize a cascade of events that may lead to CSCR through hypercoagulability and augmented platelet aggregation. In particular we investigated the role of tissue plasminogen activator, increasing plasminogen activator inhibitor 1 (PAI-1), and plasmin- 2- plasmin inhibitor complexes. We reviewed the different therapeutic approaches, including adrenergic antagonists, carbonic anhydrase inhibitors, mifepristone, ketoconazole, laser photocoagulation, intravitreal injection of bevacizumab, and photodynamic therapy with verteporfin (PDT) and our model of pathogenesis seems to be in agreement with the clinical effects obtained from these treatments. In accord with our thesis, we began to treat a group of patients affected by CSCR with low-dose aspirin (75–100 mg), because of its effectiveness in other vascular diseases and its low ocular and general toxicity with prolonged use. The formulation of a causative model of CSCR enables us to understand how the therapeutic approach cannot be based on a generalized therapy but should be individualized for each patient, and that sometimes a combined strategy of treatment is required. Moreover a complete knowledge of the disease will help to identify patients prone to the most persistent forms of CSCR, and thus help to find a treatment.Keywords: CSCR, aspirin, PAI-1, glucocorticoid, macula, pathogenesis

IntroductionCentral serous chorioretinopathy (CSCR) has been described by various names for nearly a century and a half.1–3 Despite numerous studies on this disease over the years, many aspects of CSCR remain unclear. Extensive literature describes predominantly its demography and the clinical course.4 The research has been limited by lack of homogeneity in the stage of CSCR in the cohort studies.

In general most authors have turned their attention to finding an effective strategy of treatment rather than trying to identify causes of, and contributing factors to, the occurrence of the CSCR.

Although CSCR has been described as a benign and self-limiting disease, it has a tendency to re-occur, with decreased visual function.5–7

© 2011 Caccavale et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.

Clinical Ophthalmology 2011:5 239–243

Clinical Ophthalmology Dovepress

submit your manuscript | www.dovepress.com

Dovepress 239

R E V I E W

open access to scientific and medical research

Open Access Full Text Article

DOI: 10.2147/OPTH.S17182

Central serous chorioretinopathy: a pathogenetic model

Antonio Caccavale1 Filippo Romanazzi1 Manuela Imparato1 Angelo Negri2 Anna Morano3 Fabio Ferentini2

1Department of Ophthalmology, Neuropthalmology and Ocular Immunology Service, 2Department of Ophthalmology, Hospital “C. Cantù”, Abbiategrasso, Milan, Italy; 3University Eye Clinic, Foundation IRCCS San Matteo Hospital, Pavia, Italy

Correspondence: Antonio Caccavale Hospital “C. Cantù” Abbiategrasso, 20081 Milan, Italy Tel 39 029486202 Fax 39 029486202 Email neureye@katamail.com

Abstract: Despite numerous studies describing predominantly its demography and clinical course, many aspects of central serous chorioretinopathy (CSCR) remain unclear. Perhaps the major impediment to finding an effective therapy is the difficulty of performing studies with large enough cohorts, which has meant that clinicians have focused more on therapy than on a deeper understanding of the pathogenesis of the disease. Hypotheses on the pathogenesis of CSCR have ranged from a basic alteration in the choroid to an involvement of the retinal pigment epithelium (RPE). Starting from evidence that affected subjects often present a personality prone to stress with altered pituitary–hypothalamic axis response (HPA) and that they have higher levels of serum and urinary cortisol and catecholamines than healthy subjects, we hypothesize a cascade of events that may lead to CSCR through hypercoagulability and augmented platelet aggregation. In particular we investigated the role of tissue plasminogen activator, increasing plasminogen activator inhibitor 1 (PAI-1), and plasmin- 2- plasmin inhibitor complexes. We reviewed the different therapeutic approaches, including adrenergic antagonists, carbonic anhydrase inhibitors, mifepristone, ketoconazole, laser photocoagulation, intravitreal injection of bevacizumab, and photodynamic therapy with verteporfin (PDT) and our model of pathogenesis seems to be in agreement with the clinical effects obtained from these treatments. In accord with our thesis, we began to treat a group of patients affected by CSCR with low-dose aspirin (75–100 mg), because of its effectiveness in other vascular diseases and its low ocular and general toxicity with prolonged use. The formulation of a causative model of CSCR enables us to understand how the therapeutic approach cannot be based on a generalized therapy but should be individualized for each patient, and that sometimes a combined strategy of treatment is required. Moreover a complete knowledge of the disease will help to identify patients prone to the most persistent forms of CSCR, and thus help to find a treatment.Keywords: CSCR, aspirin, PAI-1, glucocorticoid, macula, pathogenesis

IntroductionCentral serous chorioretinopathy (CSCR) has been described by various names for nearly a century and a half.1–3 Despite numerous studies on this disease over the years, many aspects of CSCR remain unclear. Extensive literature describes predominantly its demography and the clinical course.4 The research has been limited by lack of homogeneity in the stage of CSCR in the cohort studies.

In general most authors have turned their attention to finding an effective strategy of treatment rather than trying to identify causes of, and contributing factors to, the occurrence of the CSCR.

Although CSCR has been described as a benign and self-limiting disease, it has a tendency to re-occur, with decreased visual function.5–7

Clinical Ophthalmology 2011:5 submit your manuscript | www.dovepress.com

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241

Central serous chorioretinopathy: a pathogenetic model

The use of adrenergic antagonists was one of the first attempts to treat CSCR. Adrenergic antagonists reduce the effect of vasoconstriction by blocking adrenergic receptor activation induced by glucorticoids.35 In order to reduce the adrenergic tone, thought to be behind the vasospastic condition, even ablation of the stellate ganglion was used.36

Later treatment with -adrenergic antagonists was tried,37 then abandoned because of systemic side effects, and cur-rently -adrenergic antagonists are used because they have fewer side effects.38–41

Another attempt was made with the carbonic anhydrase inhibitors that act on RPE, contributing in part to the resorp-tion of the subretinal fluid.42 Recent studies show that both systemic acetazolamide and dorzolamide for topical use can increase choroidal blood flow.43–45 In the specific case of CSCR, in which a deficiency of choroidal blood flow has been described, carbonic anhydrase inhibitors could be effective.

The difficulty in predicting which patients will face a chronic and relapsing disease, resulting in impaired visual function, has led to a search for drugs that can be effective in the treatment of CSCR by reducing the activity or the serum

level of endogenous glucocorticoids. This pharmacological approach is interesting because it is directed against one of the better known factors in the genesis of the CSCR.

Mifepristone is an antagonist of glucocorticoids and progesterone receptors with a weak antiandrogen action and has a good safety and tolerability profile. In addition, mifepristone inhibits cortisol-induced peripheral vasoconstriction. Ketoconazole exerts its effects by inhibit-ing some steps in the steroid synthesis resulting in decreased levels of cortisol, androgen, and aldosterone and in elevated progesterone. These effects seem to be present at the minimum dosage of 400 mg/day. An additional action of ketoconazole is the direct antiglucocorticoid effect as an antagonist at the receptor level. Current studies on these two medications are, however, limited by the short follow-up and the number of patients recruited.46–48 Moreover, use of both mifepristone and the ketaconazole may be limited by important side effects.

As noted previously, the advent of ICGA in the study of the characteristics of choroidal circulation in patients with CSCR, and the accumulation of clinical cases of CSCR linked to systemic diseases, suggested that a disorder of choroidal blood flow could be critical in the development of the disease.

The increase in procoagulant blood factors, in particular PAI-1, was found in patients with CSCR.21,49

Moreover an increase in platelet aggregation can be induced by glucocorticoids and these factors suggested to us that a treatment that improves choriocapillaris hemody-namics and reduces PAI-1 could prevent the development of CSCR. We identified low-dose aspirin as a drug better suited for this purpose, because of its effectiveness in other vascular diseases and its low ocular and general toxicity with prolonged use.50,51 Besides its hemodynamic effects, aspirin reduces the stress response of the HPA axis, limiting the increase in serum cortisol and catecholamines.52,53 The putative mechanism of action of aspirin in the treatment of CSCR is therefore 2-fold: first, a purely hemoreologic action and, second, controlling the hyperfunction of the HPA axis. However aspirin, at greater doses, could have a paradoxical effect of vasoconstriction and predisposing to local and systemic hemorrhagic events. A dosage of 75 to 100 mg appears to be best, with a profile of effectiveness/side-effects as evidenced by extensive cardiologic trials.54,55

The pathogenetic model we have described appears to be in agreement with the effectiveness of laser photocoagula-tion and photodynamic therapy with verteporfin in selected cases of CSCR.

Increased platelet aggregation

PAI-1, tPA, plasmin-!2-plasmin inhibitor

(increased microthrombusformation and increased

hematic viscosity)Increased platelet aggregation

Relative endogenous hypercortisolism (or exogenous administration of corticoids)

Lead to

RPE DECOMPENSATION and DETACHMENT

CENTRAL SEROUS CHORIORETINOPATHY

(In cases of prolonged course of disease or when risk factors persist, CSCR can become chronic or multifocal)

Reduced choroidal flow with impaired hemorheologyand increased probability of microthrombus formation.

Lobular choriocapillaris hypoperfusion

Increased intraluminal pressure in the surroundingchoriocapillaris (Hagen–Poiseuille’s Law) with extravasation of

serum and further tamponade of microvasculature

Direct steroids vasoconstriction

Indirect vasoconstrictionmediated by sensitization to

cathecolamines

Suppression of local vasodilatorssuch

as prostacyclin and nitric oxide

Figure 1 Central serous chorioretinopathy: a pathogenetic model.Abbreviations: CSCR, central serous chorioretinopathy; PAI-1, plasminogen activator inhibitor 1; RPE, retinal pigment epithelium; tPA, tissue plasminogen activator.

Work-up endocrinologicoDosaggio cortisolo libero urinarioVisita endocrinologica

Valutazione psichiatrica

Disordini del sonno

... inoltre ...

Endocrine Abnormalities in Patients withCentral Serous Chorioretinopathy

Robert Haimovici, MD,1 Shimon Rumelt, MD,1 James Melby, MD2

Purpose: To investigate and to identify endocrine and metabolic abnormalities in patients with centralserous chorioretinopathy (CSCR).

Design: Observational case series.Participants: Twenty-four patients with CSCR.Methods: Serum and urinary catecholamines, glucocorticoids, mineralocorticoids, serum testosterone, and

thyroid-stimulating hormone (TSH) function were evaluated prospectively.Results: Fifty percent (12 of 24) of patients with active acute CSCR showed elevated 24-hour urine cortisol

or tetrahydroaldosterone levels. Serum aldosterone levels were low in 7 of 24 (29.1%) patients. Single morningplasma catecholamine levels were elevated in 7 of 24 patients, although 24-hour urine metanephrines (cate-cholamine breakdown products) were normal. Serum testosterone and TSH levels were normal in nearly all (23of 24) patients.

Conclusion: Many patients with acute CSCR have elevated 24-hour urine corticosteroids, which maycontribute to the pathogenesis of the disorder. Endogenous mineralocorticoid dysfunction is a newly describedfeature of CSCR. Ophthalmology 2003;110:698–703 © 2003 by the American Academy of Ophthalmology.

Central serous chorioretinopathy (CSCR) is a poorly under-stood disorder characterized by serous retinal detachment,retinal pigment epithelial (RPE) detachment or dysfunction,and choroidal hyperpermeability as demonstrated by fluo-rescein and indocyanine green angiography.1,2 Although thepathogenesis of the disorder is not precisely known, it isgenerally believed that glucocorticoid and possibly adren-ergic hormones play a role in the pathophysiology of CSCRand exert their effects on the retinal pigment epithelium(RPE), choroid or both.3,4 Many of the previously describedrisk factors for the disorder (including male gender,2 TypeA personality,5 psychological stress,2 pregnancy,6 history ofcorticosteroid use,7 Cushing’s syndrome,8 or steroid-pro-ducing tumors9) are conditions potentially associated withabnormal steroid regulation or male gender-specific steroidhormone regulation. A number of other hormones could

also potentially play a role in the development of CSCR.Mineralocorticoids such as aldosterone may contribute tohypertension,10,11 a known risk factor for CSCR12 Adren-ergic agents such as epinephrine (Epi) and norepinephrine(NE) are components of the stress response and couldcontribute to transient hypertension,13 choroidal vasocon-striction,14 or direct effects on the RPE.15 Both glucocorti-coids16,17 and thyroid hormone18 have been reported tosensitize the epinephrine receptors to the effects of circu-lating adrenergic hormones.Some data are available regarding corticosteroid and

adrenergic metabolism in patients with CSCR. Garg et al19examined a group of 30 patients with acute CSCR andage-matched controls. Mean morning, afternoon, and 24-hour urine cortisol levels were significantly higher in thepatient group compared with the controls, but other hor-mones were not evaluated. Wakakura and Suzuki20 foundthat urinary Epi and NE levels in patients with active CSCRwere elevated compared with controls, but further studies ofadrenergic metabolism in CSCR have not, to our knowl-edge, been performed. We therefore investigated whetherpatients with idiopathic CSCR have evidence of endocrineand metabolic dysfunction that might be considered to playa role in the pathogenesis of the disorder.

Patients and Methods

The general study design was a noncomparative, interventional,case series. A consecutive series of patients with idiopathic acuteCSCR of 6 weeks or less seen at Boston University School ofMedicine Hospitals and clinics over a period of 3-years was askedto participate in this study. Two additional patients were referredby outside physicians during the same period. All patients under-went a complete ophthalmic and medical history, examination, and

Originally received: April 29, 2002.Accepted: December 7, 2002. Manuscript no. 220303.1 Department of Ophthalmology, Boston University School of Medicine,Boston, Massachusetts.2 Endocrinology Section, Department of Medicine, Boston UniversitySchool of Medicine, Boston, Massachusetts.Presented in part at the Association for Research in Vision and Ophthal-mology annual meeting, Fort Lauderdale, Florida, May 2002.Supported by The Macula Foundation, New York, New York, and TheRichard H. Chartrand Foundation, San Francisco, California. Additionalsupport was received from Research to Prevent Blindness, New York, NewYork, and The Massachusetts Lions Eye Research Fund Inc., New Bed-ford, Massachusetts.The authors have no commercial or proprietary interest in any of thematerials noted in this article.Reprint requests to Shimon Rumelt, MD, Department of Ophthalmology,Western Galilee-Nahariya Medical Center, P.O. Box 21, 22100 Nahariya,Israel, Tel: 011-972-4-9107635, Fax: 011-972-9107611.

698 © 2003 by the American Academy of Ophthalmology ISSN 0161-6420/03/$–see front matterPublished by Elsevier Science Inc. doi:10.1016/S0161-6420(02)01975-9

were performed only in CSCR patients, and no contempo-raneous control group was tested. Statistical tests could beperformed only for the 24-hour urine cortisol and THAlevels, because data from age-matched controls were avail-able only for these parameters. Although there were meandifferences in the 24-hour urine cortisol and THA levelsbetween patients and controls, and a trend toward signifi-cance, the t test did not show these differences to be statis-tically significant. The stress questionnaire administered topatients incorporated life activity stress questions but wasnot validated in previous studies. The significance of self-reported psychologic-stress is not clear and may not bereliable, given the absence of controls. Finally, abnormalglucocorticoid or mineralocorticoid hormone levels amongthese patients certainly do not prove that they cause thedisease, although the results are plausible and are consistentwith previous animal and human studies. Despite theselimitations, this study provides an additional evidence thatendogenous corticosteroid dysfunction can be demonstratedamong a substantial percentage of patients with CSCR andmay be part in the pathogenesis of the disorder. Dysregu-lation of the renin-angiotensin-aldosterone system is alsopresent in some CSCR patients, and mineralocorticoidssuch as aldosterone and THA may be part of the pathogen-esis of CSCR. Screening for endocrine abnormalities inpatients with CSCR may reveal those amendable for endo-crine treatment.

References

1. Guyer DR, Yannuzzi LA, Slakter JS, et al. Digital indocyaninegreen videoangiography of central serous chorioretinopathy.Arch Ophthalmol 1994;112:1057–62.

2. Gass JDM. Pathogenesis of disciform detachment of the neu-roepithelium II. Idiopathic central serous choroidopathy. Am JOphthalmol 1967;63:587–615.

3. Gass JDM. Stereoscopic Atlas of Macular Diseases: Diagnosisand Treatment, 3rd ed. v. 1, St. Louis: Mosby, 1997;52–70.

4. Ciardella AP, Guyer DR, Spitznas M, Yannuzzi LA. CentralSerous Chorioretinopathy. In: Ryan S, ed. Retina. Vol.2. StLouis: Mosby, 2001;1153–81.

5. Yannuzzi LA. Type A behavior and central serous chorioreti-nopathy. Trans Am Ophthalmol Soc 1986;84:799–845.

6. Chumbley LC, Frank RN. Central serous retinopathy andpregnancy. Am J Ophthalmol 1974;77:158–60.

7. Jain IS, Singh K. Maculopathy a corticosteroid side-effect. JAll India Ophthalmol Soc 1966;14:250–2.

8. Bouzas EA, Scott MH, Mastorakos G, et al. Central serouschorioretinopathy in endogenous hypercortisolism. Arch Oph-thalmol 1993;111:1229–33.

9. Thoelen AM, Bernasconi PP, Schmid C, Messmer EP. Centralserous chorioretinopathy associated with a carcinoma of theadrenal cortex. Retina 2000;20:98–9.

10. Brown MA, Cramp HA, Zammit VC, Whitworth JA. Primaryhyperaldosteronism: a missed diagnosis in ‘essential hyper-tensives’? Aust N Z J Med 1996;26:533–8.

11. Mosso L, Fardella C, Montero J, et al. [High prevalence ofundiagnosed primary hyperaldosteronism among patients withessential hypertension]. Rev Med Chil 1999;127:800–6.

12. Tittl MK, Spaide RF, Wong D, et al. Systemic findings asso-ciated with central serous chorioretinopathy. Am J Ophthal-mol 1999;128:63–8.

13. Goldstein DS. Plasma catecholamines and essential hyperten-sion. An analytical review. Hypertension 1983;5:86–99.

14. Koss MC, Gherezghiher T. Adrenoceptor subtypes involved inneurally evoked sympathetic vasoconstriction in the anteriorchoroid of cats. Exp Eye Res 1993;57:441–7.

15. Sibayan SA, Kobuch K, Spiegel D, et al. Epinephrine, but notdexamethasone, induces apoptosis in retinal pigment epithe-lium cells in vitro: possible implications on the pathogenesisof central serous chorioretinopathy. Graefes Arch Clin ExpOphthalmol 2000;238:515–9.

16. Hadcock JR, Malbon CC. Regulation of beta-adrenergic re-ceptors by “permissive” hormones: glucocorticoids increasesteady-state levels of receptor mRNA. Proc Natl Acad SciU S A 1988;85:8415–9.

17. Sakaue M, Hoffman BB. Glucocorticoids induce transcriptionand expression of the alpha 1B adrenergic receptor gene inDTT1 MF-2 smooth muscle cells. J Clin Invest 1991;88:385–9.

18. Grassby PF, McNeill JH. Hyperthyroidism induces supersen-sitivity to biogenic amines in rat vascular tissue via a pre- anda postjunctional mechanism. J Pharmacol Exp Ther 1988;244:1027–35.

19. Garg SP, Dada T, Talwar D, Biswas NR. Endogenous cortisolprofile in patients with central serous chorioretinopathy. Br JOphthalmol 1997;81:962–4.

20. Wakakura M, Suzuki H. Urinary excretion of catecholaminesin central serous chorioretinopathy. Jpn J Clin Ophthalmol1979;33:1237–40.

21. Spaide RF, Campeas L, Haas A, et al. Central serous chori-oretinopathy in younger and older adults. Ophthalmology1996;103:2070–9; discussion 2079–80.

22. Spaide RF, Hall L, Haas A, et al. Indocyanine green video-angiography of older patients with central serous chorioreti-nopathy. Retina 1996;16:203–13.

23. Janzer RC, Raff MC. Astrocytes induce blood–brain barrierproperties in endothelial cells. Nature 1987;325:253–7.

24. Arndt C, Sari A, Ferre M, et al. Electrophysiological effects ofcorticosteroids on the retinal pigment epithelium. Invest Oph-thalmol Vis Sci 2001;42:472–5.

25. Dohrmann J, Lommatzsch A, Spital G, Pauleikhoff D. [Patho-genesis of central serous chorioretinopathy: angiographic and

Table 1. Endocrine Abnormalities in Patients with CentralSerous Chorioretinopathy

Endocrine Findings

No. ofPatients

(24 Patients)

CortisolElevated serum cortisol levels 0 (0%)Elevated 24-hour urine cortisol 9 (38%)Abnormal diurnal pattern of cortisol secretion 7 (29%)

Aldosterone and tetrahydroaldosteroneElevated 24-hour urine THA 7 (29%)Elevated 24-hour urine cortisol and THA 4 (17%)Low serum aldosterone 7 (29%)

Adrenergic hormonesElevated random plasma epinephrine 4 (16%)Elevated random plasma norepinephrine 3 (13%)Elevated 24-hour urine for metanephrines 0 (0%)

Note: Number of findings exceed patient numbers because of multipleabnormalities in some patients.THA ! tetrahydroaldosterone.

Ophthalmology Volume 110, Number 4, April 2003

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Horniker E. Su di una forma di retinite centrale di origine vasoneurotica. Ann Oftalmol 1927

Zeligs MA. Central angiospastic retinopathy. A psychosomatic study of its occurrence in military personel. Psychosom Med 1947

Harrington DO. Psychosomatic interrelationship in ophthalmology. Am J Ophthalmol 1948

Lipowski ZJ et al. Psychosomatic aspects of central serous retinopathy: a review and case report. Psychosomatics 1971

CLINICAL SCIENCE

Psychosomatic aspects in patients with central serouschorioretinopathyC Spahn, J Wiek, T Burger, L Hansen. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Br J Ophthalmol 2003;87:704–708

Aims: Patients with central serous chorioretinopathy were tested for psychosomatic symptoms andsocial support at the onset of their ailments; their personality profiles were also tested.Methods: 24 consecutive outpatients at the department of ophthalmology, Freiburg University Hospi-tal, Freiburg, Germany, presenting with central serous chorioretinopathy filled in the following stand-ardised questionnaires: Symptom Checklist 90-R (SCL 90-R), Symptom List, Questionnaire on SocialSupport, and Sixteen Personality Factor Questionnaire.Results: The sample (n=24) included 22 male patients with an average age of 44.1 years. Threequarters of the patients have children and live with their families; three quarters are white collar work-ers or self employed; one quarter are skilled blue collar workers. 12 patients were suffering from theailment for the first time; 12 patients were undergoing a relapse. Mean visus of the affected eye was0.8. The Symptom List yielded an inconspicuous total score for psychosomatic symptoms. In the SCL90-R, nine out of 24 patients (37%) evinced elevated psychic stress. The total value of the questionnaireon social support showed good social support. In the Sixteen Personality Factor Questionnaire, thepatients showed heightened emotional instability and insecurity as well as flexibility and spontaneity.Conclusion: The sociodemographic data confirm that central serous chorioretinopathy ispredominantly an ailment of middle aged, socially well integrated men. This study suggests elevatedpsychic stress a few weeks after the onset of the ailment. The personality factors in the patients withcentral serous chorioretinopathy found in this study have to be verified with other populations. Theseresults did not clearly show that psychosocial factors have a definite role in the aetiology of centralserous chorioretinopathy. In order to make any clear assertions about this matter, further longitudinalstudies on the progression of psychosocial parameters with larger patient samples would be indispen-sable.

Since the original description of central serous chorio-retinopathy (CSC) by von Graefe in 1866,1 a variety ofaetiological factors and pathophysiological mechanisms

have been discussed.2 The aetiology of CSC remains unclear tothis day.3 Psychosomatic aspects of the ailment were pointedout long ago.4 Harrington5 and Zeligs6 reported a relativelyhigh incidence of CSC among American naval personnel dur-ing the second world war. It was suggested that anxiety andacute psychological trauma have a definite role in precipitat-ing the ocular disorder.5–8 In subsequent studies, it was shownthat a high proportion of those suffering from CSC are youngmen.5–10

In the 1970s, Werry and Arends11 described a neurotic per-sonality structure in patients with CSC which could not, how-ever, be confirmed by later studies.12 13 A further study associ-ated CSC with type A behaviour.10 Contradictory evidence hasalso been gathered regarding the number of life events beforethe onset of CSC.12 14–16 In the largest study with 230 patients,Tittl et al17 found psychopharmacological medication use(anxiolytic and antidepressive medication among 13% of thepatients), corticosteroid use, and hypertension as factorsassociated with CSC. The authors speculate that increasedsympathetic nervous system stimulation created by psycho-logical stress may induce CSC.17 However, in this studypsychological symptoms of the patients were not directlyexplored. In other studies, larger numbers of psychologicaland physical symptoms as well as lower social support werefound in patients with CSC.12 13 15 Altogether, investigationsconducted until now on the subject of psychosomatic aspectsof CSC have yielded inconsistent results.

In the present study, psychosomatic symptoms at the timeof onset of the ailment as well as the personality profile of

patients with CSC were investigated in order to improve theevidence regarding these psycho-ophthalmological questions.

METHODSPatientsBetween July 1999 and September 2001, all patients (n=31)at the department of ophthalmology, Freiburg University Hos-pital, Freiburg, Germany, presenting with the diagnosis ofcentral serous chorioretinopathy were consecutively enrolledin the study. After a complete ophthalmological examination(Snellen visual acuity, slit lamp, funduscopy) the diagnosiswas based on typical symptoms (visual decrease, metamor-phopsia) and findings (serous retinal elevation) and was con-firmed by fluorescence angiography (leaking point). Thepatients were asked at least within 6 weeks after the initialonset of the symptoms to complete standardised psychometricquestionnaires; 24 out of 31 patients (77.4%) answered thequestionnaires. The main reasons for non-participation werefear of disclosure of private issues and negative attitudetowards research. Table 1 shows the comparison between thepatients included and the refusers. Among the respondingpatients there were more patients with a relapse of the CSCand the responding patients were, on the average, 7 yearsolder.

As only standardised questionnaire instruments wereemployed, we used the available norm and comparative sam-ple values instead of a control group.

The study was approved by the ethics review committee ofFreiburg University. Informed consent was given by allsubjects.

See end of article forauthors’ affiliations. . . . . . . . . . . . . . . . . . . . . . .

Correspondence to:Claudia Spahn, MD,Abteilung fürPsychosomatik undPsychotherapeutischeMedizin, UniversitätsklinikFreiburg, Hauptstrasse 8,D-79104 Freiburg,Germany;Claudia.Spahn@klinikum.uni-freiburg.de

Accepted for publication19 November 2002. . . . . . . . . . . . . . . . . . . . . . .

704

www.bjophthalmol.com

group.bmj.com on December 1, 2012 - Published by bjo.bmj.comDownloaded from

4 questionari validati

37% dei pazienti: stress psichico elevatoElevata instabilità emozionale ed insicurezza associate a flessibilità e spontaneità

Proposta nel 2003 da Yannuzzi

Principale indicazione: CRSC cronica

RazionaleVasocostrizione coriocapillareReazione infiammatoria nello spazio sottoretinico > adesione neuroretina a EPR

PDT

Risultati a 4 anni (46 occhi di 42 pz. con CRSC >6 mesi) pubblicati nel 2012 (Silva et al Retina 2012)

Miglioramento AV: 74%Peggioramento AV: 9%Riassorbimento liquido: 93%No assottigliam. neuroretina

PDT

Nessun caso diAtrofia EPRRottura EPRCicatrici corioretinicheIpoperfusione coroide

PDT

PHOTODYNAMIC THERAPY FORCHRONIC CENTRAL SEROUSCHORIORETINOPATHYA 4-Year Follow-up Study

RUFINO M. SILVA, MD, PHD,*†** JOSE M. RUIZ-MORENO, MD, PHD,‡ FRANCISCO GOMEZ-ULLA, MD,PHD,§ JAVIER A. MONTERO, MD,¶ TATIANA GREGÓRIO, MD,*† MARIA L. CACHULO, MD,*†ISABEL A. PIRES, MD,*† JOSÉ G. CUNHA-VAZ,† JOAQUIM N. MURTA, MD*†**

Purpose: To evaluate the efficacy and safety of standard photodynamic therapy withverteporfin at 48 months in patients with chronic central serous chorioretinopathy.

Methods: A retrospective, multicenter, interventional case series analysis in patients withchronic central serous chorioretinopathy, treated with standard photodynamic therapy, andwith$4 years of follow-up. Evaluations were performed every 3 months in the first year, every6 months in the second year, and thereafter annually. Optical coherence tomography wasperformed in all visits. Fluorescein angiography and indocyanine green angiography wereperformed at baseline and thereafter as necessary. Retinal thickness on optical coherencetomography was measured manually, evaluating central macular thickness and neural retinathickness. Main outcomes included the evolution of best-corrected visual acuity, the resolu-tion of subretinal fluid, documented with optical coherence tomography, the number of treat-ments, and the evaluation of neural retina thickness during the 48 months of follow-up.

Results: The study included 46 eyes of 42 patients, 38 men (90.4%) and 4 women (9.5%),with mean age of 49.19 ± 9.9 years (range, 32–70 years), and the minimal follow-up period was48 months (mean, 56.8 ± 10.3 months). Subretinal fluid was observed in all the included eyesat baseline, and 10 eyes (21.7%) had intraretinal diffuse or cystoid fluid. Concerning the meanbest-corrected visual acuity, a statistically significant improvement (P , 0.01, Student t-test)was registered from 58.8 ± 18.3 letters at baseline to 66.9 ± 18.6 letters at 48th month.A complete resolution of subretinal fluid was achieved in 93.4%, and resolution of intraretinalfluid occurred in all 10 cases at 48 months. Neural retina thickness remained stable during the48 months of follow-up (163.8 ± 47 mm at baseline and 163.8 ± 46 mm at 48 months). Themean number of treatments was 1.08 ± 0.3. No systemic or ocular side effects were registered.

Conclusion: Standard photodynamic therapy with verteporfin was effective and safe inchronic central serous chorioretinopathy treatment with a significant improvement in thelong term, both anatomic and visual, without inducing additional retinal atrophy or systemicadverse effects.

RETINA 0:1–7, 2012

Central serous chorioretinopathy (CSC) is character-ized by an idiopathic serous retinal detachment in

the posterior pole associated with one or more leaksfrom the level of the retinal pigment epithelium (RPE).1

Gass2 proposed, in 1967, choriocapillaris hyperperme-ability as the primary cause of CSC. Many years later,multiple reports described multifocal areas of choroidalvascular hyperpermeability in CSC patients, usingindocyanine green angiography (ICG-A).1,3–6

Central serous chorioretinopathy usually resolveswithout treatment and has a good prognosis, with normal

vision often returning within a few months.7 However,visual loss or permanent symptoms may occur in caseswith persistent focal leakage or chronic diffuse leakage.8

Treatment should be considered after 3 months withoutresolution of acute CSC and in chronic CSC.8,9 A pilotstudy, performed by Yannuzzi et al10 in 2003, showedthat ICG-A–guided photodynamic therapy (PDT) withverteporfin could be safe and effective for treatingchronic CSC. The rationale for verteporfin PDT is thatangioocclusive treatment may lead to narrowing of cho-roidal vessels, thereby reducing choroidal exudation

1

Copyrightª by Ophthalmic Communications Society, Inc. Unauthorized reproduction of this article is prohibited.

Necessità 2° trattamento PDT8.6% (Silva et al Retina 2012)

15.9% (Ruiz-Moreno et al Acta Ophthalmol 2010)

12.5% (Cardillo Piccolino et al Retina 2003)

27.3% (Tarantola et al Lasers Surg Med 2008)

Ricomparsa liquido dopo osservazione o laser focale: 40%

PDT

Altri studi hanno riportato casi diAtrofia EPR (Cardillo Piccolino et al Retina 2003)

Neovasi coroideali (Chan et al BJO 2003,

Colucciello Retina 2006)

Ischemia coriocapillareRiduzione transitoria funzione maculare (scotoma soggettivo x 2 gg, elettrofisiologia)

PDT

Dosaggi tradizionali = rischio di ulteriore danno all’EPR

PDT

Metà fluenzaMetà dose

Ciardella

PDT

Dose piena

Metà fluenza Metà dose

Fluenza 50 J / cm2 25 J / cm2 50 J / cm2

Dose 6 mg / m2 6 mg / m2 3 mg / m2

No differenze fra PDT standard e metà fluenza per:

Riassorbimento liquido (100% vs 94.1%)AVSpessore fovea (Stratus OCT)

Minore ipoperfusione coriocapill.

PDT

(Shin et al Retina 2011)

No differenze fra PDT standard e metà fluenza per:

Riassorbimento liquido (79% vs 91%)AV

Migliori dati alla microperimetria con metà fluenza

PDT

(Reibaldi et al AJO 2011)

PDT metà fluenzaUtilizzata con successo anche nella CRSC acuta100% riassorbimento liquido a 1 mese e fino a 12 mesiNessuna complicanza retinica

PDT

(Smretschnig et al Retina 2012)

PDT metà dose:Utile nella CRSC cronicaRiassorbimento liquido: 85% a 1 mese e 89.6% a 12 mesiMiglioramento AV da 20/40 a 20/30Risultati peggiori negli occhi con distacco EPR

PDT

(Lai et al BJO 2006, Chan et al Retina 2008)

PDT metà dose:Rischio recidiva in circa 10% casiRecidiva distacco EPR >20% entro un anno

PDT

(Shinojima et al Retina 2011)

PDT metà dose:Utile anche nella CRSC acuta

Migliori risultati vs. Placebo per:Riassorbimento liquido (95% vs 58%)AV

PDT

(Chan et al Ophthalmology 2008)

DomandeQuale dei 3 regimi è il migliore?Risultati migliori se la CRSC è trattata prima (fase acuta)?Risultati peggiori se ICGA non mostra aree di iperpermeabilità dela coroide?

PDT

PDT: terapia più studiata e con migliori risultati. Complicanze rare

Avastin: pochi studi e molti dubbi

Farmaci: pochi studi e poche prove...

Conclusioni