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Central Serous Retinopathy Update: Diagnostic and Treatment Highlights

Retinal Physician March 1, 2010

Central Serous Retinopathy Update: Diagnostic and Treatment Highlights

MICHAEL COLUCCIELLO, MD

There have been several new findings in the diagnostic evaluation and treatment of central serous retinopathy (CSR) since it was last featured in this magazine in September 2008.1 In that review, I presented the epidemiology, pathophysiology, clinical presentation, evaluation, natural history and differential diagnosis, as well as the treatment options available. In this update, I present new developments in diagnostic evaluation and treatment of CSR.

DIAGNOSIS

• Optical Coherence Tomography. Spectral-domain high-resolution (5-8 µm) raster-scanning optical coherence tomography has allowed us to appreciate more subtle changes in patients with CSR. SD-OCT demonstrated discrete changes in reflectivity within the outer nuclear or plexiform layers and multiple small pigment epithelial detachments in more than 60% of patients in one study. Subretinal fluid may not be associated with the loss of photoreceptor layer integrity and deposits were noted beneath the outer column segments in that study2 In another study, the OCT ophthalmoscope demonstrated precipitates on the posterior surface of the detached retina, as well as in the outer retinal layer, in patients with CSR. The authors felt that intraretinal precipitates may result from proteins or accumulation of macrophages that may have phagocytized photoreceptor outer segments.3

An important study utilizing SD-OCT demonstrated that the outer nuclear layer thickness was positively correlated with the best corrected visual acuity in resolved CSR. Lower visual acuity and thinner outer nuclear layer were often associated with discontinuity of the inner segment/outer segment junction line.4

Figure 1. Deposits (asterisk) posterior to the photoreceptors and anterior to subretinal fluid in a patient with CSR.

Positioning an SD-OCT device very close to the eye allows one to acquire an inverted image. This inverted image can be utilized to evaluate choroidal thickness (so-called “enhanced depth imaging”). One study demonstrated a very thick choroid in patients with CSR.5 Based on this finding, the authors theorized that CSR may be caused by increased hydrostatic pressure in the choroid, compared to normal individuals. This may lead to choroidal hyperpermeability, and this proposed pathogenetic mechanism has therapeutic implications.

SD-OCT has also demonstrated changes in the RPE in the asymptomatic eye of CSR patients with unilateral exudative retinal detachment. Three-dimensional single-layer RPE maps showed RPE bumps in 94% of asymptomatic eyes and pigment epithelium detachment in 11.8% of asymptomatic eyes in patients with CSR.6

OCT imaging techniques allow us to make observations in patients with chronic CSR. In one study, “posterior cystoid retinal degeneration” (cystoid changes occurring where the retina adhered to subretinal fibrosis or atrophy of the RPE in choroid) were seen in eyes with chronic CSR.7 This pattern was distributed outside the fovea and was not necessarily associated with reduced visual acuity. The same investigators showed in another study that the development of posterior cystoid retinal degeneration was associated with subretinal fibrosis; these patients tended to have symptom duration longer than five years.8

Figure 2. Acute CSR showing PED with discontinuous RPE (arrow), possibly indicating areas of RPE leakage, with overlying exudative neurosensory retinal detachment (asterisk).

Other newer observations included an RPE tear following CSR9 and atypical CSR with peripapillary subretinal fluid, suggesting an optic neuropathy.10 An OCT study showed that outer nuclear layer thickness was significantly higher in patients with rhegmatogenous retinal detachment (RRD) compared to patients with exudative retinal detachment associated with acute CSR — perhaps accounting for the worse visual function in RRD compared to CSR.11

• Multifocal Electroretinography. A study using multifocal electroretinography indicated that the height of serous macular detachment in CSR correlated with the impairment in the conduction of electrical responses in the paracentral macula (by measurement of N1 and P1 latencies).12

• Microperimetry. In acute CSR, microperimetry may quantify central macular function; microperimetry may supplement OCT findings and correlate anatomical and functional changes.13 After resolution of CSR, macular regions with irregularity of the RPE or defects of the photoreceptor inner segment/outer segment junction on OCT demonstrate focal areas of reduced retinal function on microperimetry.14

• Fundus Autofluorescence and Retinal Flavoprotein Fluorescence. Fundus autofluorescence has played an increased role in determining dysfunctional RPE cells. Areas of RPE atrophy show decreased autofluorescence due to the absence of fluorophores, which usually reside in RPE lipofuscin granules. Increased autofluorescence may be associated with an increased amount of lipofuscin, which may presage RPE atrophy. One observational study demonstrated a focal decrease in fundus autofluorescence at the leakage site in most cases of acute CSR, along with an increase in autofluorescence in the region of the retinal detachment.15 Another study demonstrated that this autofluorescence increase normalized following photodynamic therapy treatment.16

Figure 3. Early (left) and late (right) images of acute CSR demonstrating a classic “smoke-stack” RPE leak of the FA image insert on top of a photo showing the exudative RD.

Retinal flavoprotein fluorescence (using 467-nm excitation and 535-nm emission filters) is a measurement of metabolic tissue stress. Cells with stressed mitochondria develop impaired electron transport, which causes more flavoprotein in the chain to be oxidized. These oxidized flavoproteins emit green autofluorescence upon absorption of blue light, which can be measured. Measured retinal flavoprotein fluorescence is significantly higher in eyes affected with CSR, indicating increased metabolic stress in these cases.17

ASSOCIATED CONDITIONS

• Steroids. New reports further solidify the association of steroids and the development of CSR.

Intra-articular corticosteroid injections are very common in the orthopedic arena. Although complications from these injections are uncommon, separate case reports have been published that have shown an association between a glenohumeral corticosteroid injection and CSR18 and a knee joint intra-articular steroid injection and CSR.19

CSR may also arise as a complication of intravitreal steroid (triamcinolone acetonide) injection. A case report was published describing such an occurrence following intravitreal triamcinolone injection for treatment of a branch retinal vein occlusion.20

A recent case control study conducted in 23 patients with central serous retinopathy (and 12 patients who serve as controls) demonstrated that CSR was associated with elevated 8:00 AM serum cortisol levels.21

• CSR and the Performance of Ophthalmologic Procedures. Recent case studies that associate CSR with the performance of ophthalmic procedures may be explained on the basis of stress-induced increased cortisol levels in susceptible individuals: CSR has been associated with the performance of LASIK for hyperopia,22 dacryocystorhinostomy,23 and sequential laser argon ng-YAG iridotomies.24

Glaucoma and ocular hypertension appeared to be less frequent in CSR patients than controls in another study.25

• H. pylori and Central Serous Retinopathy. As indicate in the review article from the fall of 2008, Helicobacter pylori may be associated with CSR. In one study, H. pylori infection was statistically more frequent among patients with CSR than in the control group.26 In another study by the same investigators, H. pylori infection was detected using the urease test and histopathological examination in 11 of 14 patients with clinically determined CSR.27

• CSR and the Use of PDE-5 Inhibitors. There are ongoing concerns regarding CSR and the use of phosphodiesterase-5 (PDE-5) inhibitors. In one study, patients with CSR had no increase in prescription exposure to PDE-5 inhibitors than did age-matched control subjects.28 In another study, CSR recurred in three of six patients when attempting to resume sildenafil (Viagra, Pfizer) therapy after cessation was associated with improvement in vision.29 A causal relationship between administration of PDE-5 inhibitors and CSR can still not be established.

TREATMENT

Withdrawal of exogenous steroids and observation continue to be appropriate first-line treatments for acute CSR, since the natural history allows for spontaneous resolution within three months in 80 to 90% of affected individuals.

Ongoing studies of various agents and modalities have disclosed some interesting findings. Laser photocoagulation, PDT, bevacizumab and other medications, and treatment of associated conditions have all shown promise.

• Subthreshold Micropulse Diode Laser and “Selective” Laser Treatment. Subthreshold micropulse diode laser (810 nm) has demonstrated efficacy in three small studies in patients with focal leakage to photocoagulate the leaking site.30-32 Indocyanine green dye was used to enhance the subthreshold diode laser micropulse photocoagulation in seven patients with chronic CSR who had no spontaneous resolution six months after onset in another study. All patients had resolution of the neurosensory retinal detachment without recurrence at 12 months follow-up.33

“Selective laser treatment” has also been attempted. In one study, one year postoperative follow-up of patients undergoing selective laser treatment (527 nm, pulse duration 200 nsec [30 pulses at 100 Hz]; energy 100 to 200 µJ per pulse; retinal spot diameter 200 µm) showed no collateral retinal damage by SD-OCT — unlike those patients undergoing conventional laser photocoagulation (532 nm; power 100 to 200 mW; retinal spot diameter 100 µm; pulse duration 100 msec).34

• Photodynamic Therapy: “Standard” and “Half-fluence” Doses. Photodynamic therapy to treat CSR continues to be studied in both the acute and chronic presentations. PDT may allow for cessation of RPE leaks in CSR by causing choriocapillaris hypoperfusion in the near term, followed by choroidal vascular remodeling, preventing recurrence.

One-year results of a randomized controlled trial “half-dose” (3 mg per square meter) verteporfin PDT for acute CSR demonstrated a decided advantage in the treatment group: 37 of 39 verteporfin treated eyes, compared with 11 of 21 eyes in the placebo group, showed absence of subretinal fluid at the macula at 12 months. This difference (95% vs 58%) was highly statistically significant (P=.001).35

Other studies utilizing PDT concentrated on patients with chronic CSR. One retrospective review demonstrated complete resolution of serous retinal detachment (mean duration of symptoms 27 months) in nine of 11 eyes with conventional PDT36 Another study demonstrated resolution of macular detachment and subretinal fluid in all 82 eyes with chronic CSR treated with conventional “full-fluence” PDT, with no complications and a mean follow-up of 12 months.37 A third study of 41 eyes treated with conventional PDT for CSR demonstrated complete resolution of serous fluid on OCT performed within six weeks after PDT in 88% of the eyes.38 In that study, visual improvement appeared to be limited in patients with RPE atrophy, foveal outer segment/intersegment disintegrity, and prolonged symptom duration.

Low-fluence (“half-fluence,” 25 J/cm2 at an irradiance of 300 mW) PDT has been studied for treatment of chronic CSR. In one such study, two patients with a history of chronic CSR lasting more than 10 years demonstrated complete resolution of subretinal fluid at one and nine months after low-fluence PDT39 Another chronic CSR treatment study involved 19 eyes treated with standard-fluence PDT and 23 eyes with treated with low-fluence PDT. In most of the eyes (79% with standard treatment and 91% with low-fluence treatment), PDT resulted in complete subretinal fluid absorption and visual acuity improvement. It appeared as if choroidal hypoperfusion related to PDT could be reduced by low-fluence treatment compared to full-fluence treatment (choriocapillaris non-perfusion was seen in eight standard-fluence–treated eyes but in no low-fluence–treated eyes).40

One additional report describes three patients with severe choroidal ischemia and one with choroidal neovascularization in the treatment area following standard-dose PDT treatment for chronic CSR.41 However, complications still may occur with half fluence PDT: a single case report describes an RPE tear occurring after half-fluence PDT treatment of chronic CSR.4

• Bevacizumab. The anti-vascular endothelial growth factor antibody bevacizumab also continues to be used to attempt to treat both acute and chronic CSR. Bevacizumab has significant antipermeability properties; as described above, choroidal vascular hyperpermeability may play a role in the genesis of CSR.

Three recent uncontrolled studies involved treatment of acute CSR with bevacizumab. One used a single dose of 2.5 mg bevacizumab. In this study involving five eyes,43 complete resolution of subretinal fluid ensued. Another two studies of treatment of acute CSR used a single dose of 1.25 mg bevacizumab — one involving six eyes,44 and another study of 10 patients.45 All patients promptly showed resolution of neurosensory retinal detachment.

In one series utilizing 2.5 mg bevacizumab intravitreal injections to treat chronic CSR, 12 patients were treated at six- to eight-week intervals until intraretinal and subretinal fluid resolved. After a mean follow-up of 24 weeks, patients received on average approximately two intravitreal injections of bevacizumab. Six patients showed complete resolution of subretinal fluid.46

• Treatment of Obstructive Sleep Apnea Syndrome. Observational case reports have demonstrated resolution of CSR after treatment of obstructive sleep apnea syndrome. In one series, 22% of 56 consecutive patients with acute CSR suffered from obstructive sleep apnea syndrome, whereas in the general population, obstructive sleep apnea is much less frequently reported (2% to 4%).47 Another published case demonstrated rapid resolution of bilateral CSR with treatment of newly diagnosed obstructive sleep apnea.48 Clinicians should consider this diagnosis in patients with CSR and refer when appropriate.

• Helicobacter pylori and CSR. Although not currently widely considered in the United States, the results of the studies showing an association between H. pylori and CSR suggest that we should bear in mind the possibility of H. pylori infection in patients with CSR. If larger randomized controlled studies demonstrate further evidence of this association, there would obviously be a large impact on the evaluation and management of CSR (ie, urease breath test and H. pylori serology for diagnosis, and “triple” [or “quadruple”] therapy [eg, omeprazole, antibiotics, and bismuth subsalicylate] for treatment).

• Ketoconazole. In the earlier summary, it appeared as if ketoconazole showed some promise for the treatment of CSR. Ketoconazole is an antifungal that is also an adrenocorticoid antagonist. Unfortunately, in a more recent small study of 15 consecutive patients treated with ketoconazole 200 mg a day for four weeks with 15 patients serving as a control group, there was no statistically significant difference in anatomical or functional improvement between the two groups.49 So although decreasing endogenous cortisol synthesis appears to be a rational approach, in this study ketoconazole did not appear to offer benefit.

• Mifepristone. Mifepristone, a progesterone and glucocorticoid antagonist, has shown some promise, as indicated in the earlier review. A more recent follow-up of the patient in this study demonstrated that a recurrence was unresponsive to PDT, but was dramatically responsive to repeat challenge with mifepristone 200 mg daily for 90 days.50 This repeat favorable clinical and anatomical response warrants further investigation. However, the high cost of treatment (approximately $200 for a 200-mg dose) will hinder the general usage of this modality.

Figure 4. FA insert overlay on color photograph of a case of CSR with exudative RD and punctuate precipitates.

Figure 5. RPE leak temporal to disc (FA overlay) with CSR RD extending into fovea.

• Acetylsalicylic Acid. Finally, acetylsalicylic acid has been studied in treatment of CSR. Use of aspirin is based on the finding that plasminogen activator inhibitor-1 may be increased in CSR patients. Aspirin is effective in lowering plasminogen activator inhibitor-1 levels and platelet aggregation. In a study of 107 patients given 100 mg aspirin daily for a month and 100 mg every other day for five months, VA improved and then remained stable to the end of the follow-up (median 20 months). VA improved after the first week. This study gave no anatomical details (eg, no OCT data), and there was no control group.51

SUMMARY

In summary, improved diagnostic modalities will allow clinicians to evaluate patients with CSR with increased sensitivity. Although the natural history of CSR is good, there does occur visual disability for a period of time in these patients, who frequently have high visual demands. In the near future, it appears as if clinicians will have a variety of interventions at their disposal that may allow for a more rapid resolution of neurosensory retinal detachment and improvement in vision and functional ability in patients affected with this disease. RP

Michael Colucciello, MD, is a clinical associate in the Department of Ophthalmology at the University of Pennsylvania School of Medicine in Philadelphia and a retina specialist practicing with South Jersey Eye Physicians in Moorestown, NJ. He reports no financial interests in products mentioned in this article. Dr. Colucciello can be reached via e-mail at michael@macula.us.

REFERENCES

  1. Colucciello M. Central serous retinopathy. Retinal Physician. 2008;5(7):26-34.
  2. Ahlers C, Geitzenauer W, Stock G, et al. Alterations of intraretinal layers in acute central serous chorioretinopathy. Acta Ophthalmol. 2009;87:511-516.
  3. Kon Y, Iida T, Maruko I, et al. The optical coherence tomography-ophthalmoscope for examination of central serous chorioretinopathy with precipitates. Retina. 2008;28:864-869.
  4. Matsumoto H, Sato T, Kishi S. Outer nuclear layer thickness at the fovea determines visual outcomes in resolved central serous chorioretinopathy. Am J Ophthalmol. 2009;148:105-110.e1.
  5. Imamura Y, Fujiwara T, Margolis R, et al. Enhanced depth imaging optical coherence tomography of the choroid in central serous chorioretinopathy. Retina. 2009;29:1469-1473.
  6. Gupta P, Gupta V, Dogra MR, et al. Morphological changes in the retinal pigment epithelium on spectral-domain OCT in the unaffected eyes with idiopathic central serous chorioretinopathy. Int Ophthalmol. 2009 Jan 30. [Epub ahead of print]
  7. Piccolino FC, De La Longrais RR, Manea M, et al. Posterior cystoid retinal degeneration in central serous chorioretinopathy. Retina. 2008;28:1008-1012.
  8. Piccolino FC, De La Longrais RR, Manea M, et al. Risk factors for posterior cystoid retinal degeneration in central serous chorioretinopathy. Retina. 2008; 28:1146-1150.
  9. Gueudry J, Genevois O, Adam PA, et al. Retinal pigment epithelium tear following central serous chorioretinopathy. Acta Ophthalmol. 2009;87:691-693.
  10. Johnson D. Atypical central serous chorioretinopathy with peripapillary subretinal fluid suggesting an optic neuropathy. J Neuroophthalmol. 2009;29:155-156.
  11. Maruko I, Iida T, Sekiryu T, et al. Morphologic changes in the outer layer of the detached retina in rhegmatogenous retinal detachment and central serous chorioretinopathy. Am J Ophthalmol. 2009;147:489-494.e1.
  12. Yip YW, Ngai JW, Fok AC, et al. Correlation between functional and anatomical assessments by multifocal Electroretinography and optical coherence tomography in central serous chorioretinopathy. Doc Ophthalmol. 2010 Jan 12. [Epub ahead of print]
  13. Dinc UA, Yenerel M, Tatlipinar S, et al. Correlation of retinal sensitivity and retinal thickness in central serous chorioretinopathy. Ophthalmologica. 2010; 224:2-9.
  14. Ojima Y, Tsujikawa A, Hangai M, et al. Retinal sensitivity measured with the microperimeter 1 after resolution of central serous chorioretinopathy. Am J Ophthalmol. 2008;146:77-84.
  15. Ayata A, Tatlipinar S, Kar T, et al. Near-infrared and short-wavelength autofluorescence imaging in central serous chorioretinopathy. Br J Ophthalmol. 2009; 93:79-82.
  16. Ozmert E, Batioğlu F. Fundus autofluorescence before and after photodynamic therapy for chronic central serous chorioretinopathy. Ophthalmologica. 2009;223:263-268.
  17. Field MG, Elner VM, Park S, et al. Detection of retinal metabolic stress resulting from central serous retinopathy. Retina. 2009;29:1162-1166.
  18. Hurvitz A P, Hodapp KL, Jadgchew J, et al. Central serous chorioretinopathy resulting in altered vision and color perception after glenohumeral corticosteroid injection. Orthopedics. 2009;32(8). pii: orthosupersite.com/view.asp?rID=41926.
  19. Balakrishnan S, Apsingi S, Manjure SB. Sudden loss of visual acuity following intra-articular steroid injection in to the knee joint: a case report. Cases J. 2008;1:428.
  20. Kocabora MS, Durmaz S, Kandemir N. Exacerbation of central serous chorioretinopathy following intravitreal triamcinolone injection. Graefes Arch Clin Exp Ophthalmol. 2008;246:1783-1786.
  21. Zakir SM, Shukla M, Simi ZU, et al. Serum cortisol and testosterone levels in idiopathic central serous chorioretinopathy. Indian J Ophthalmol. 2009; 57:419-422.
  22. Lim MC, Chan TK. Central serous chorioretinopathy following LASIK for hyperopia. J Refract Surg. 2008;24:651-652.
  23. Mondal L, Basu S, Baidya K, et al. Central serous chorioretinopathy after dacryocystorhinostomy operation on the same side. Indian J Ophthalmol. 2009;57:57-58.
  24. Liu DT, Fan AH, Li CL, et al. Central serous chorioretinopathy after sequential argon-neodymium: YAG laser iridotomies. Ophthalmic Surg Lasers Imaging. 2009;40:177-179.
  25. Imamura Y, Fujiwara T, Spaide RF. Frequency of glaucoma in central serous chorioretinopathy: a case-control study. Retina. 2010;30:267-270.
  26. Misiuk-Hojło M, Michałowska M, Turno-Krecicka A. Helicobacter pylori—a risk factor for the developement of the central serous chorioretinopathy. Klin Oczna. 2009;111:30-32.
  27. Kmera-Muszyńska M, Wójcicka I, Muszyski J. [Is Helicohacter pylori infection associated with CSR occurrence?]. Klin Oczna. 2008;110:273-276.
  28. French DD, Margo CE. Central serous chorioretinopathy and phosphodiesterase-5 inhibitors: a case-control postmarketing surveillance study. Retina. 2010;30:271-274.
  29. Fraunfelder FW, Fraunfelder FT. Central serous chorioretinopathy associated with sildenafil. Retina. 2008;28:606-609.
  30. Chen SN, Hwang JF, Tseng L F, et al. Subthreshold diode micropulse photocoagulation for the treatment of chronic central serous chorioretinopathy with juxtafoveal leakage. Ophthalmology. 2008;115:2229-2234.
  31. Lanzetta P, Furlan F, Morgante L, et al. Nonvisible subthreshold micropulse diode laser (810 nm) treatment of central serous chorioretinopathy. A pilot study. Eur J Ophthalmol. 2008;18:934-940.
  32. Gupta B, Elagouz M, McHugh D, et al. Micropulse diode laser photocoagulation for central serous chorio-retinopathy. Clin Experiment Ophthalmol. 2009; 37:801-805.
  33. Ricci F, Missiroli F, Regine F, et al. Indocyanine green enhanced subthreshold diode-laser micropulse photocoagulation treatment of chronic central serous chorioretinopathy. Graefes Arch Clin Exp Ophthalmol. 2009;247:597-607.
  34. Framme C, Walter A, Prahs P, et al. Structural changes of the retina after conventional laser photocoagulation and selective retina treatment (SRT) in spectral domain OCT. Curr Eye Res. 2009;34:568-579.
  35. Chan WM, Lai TY, Lai R Y, et al. Half-dose verteporfin photodynamic therapy for acute central serous chorioretinopathy: one-year results of a randomized controlled trial. Ophthalmology. 2008;115:1756-1765.
  36. Tarantola RM, Law JC, Recchia FM, et al. Photodynamic therapy as treatment of chronic idiopathic central serous chorioretinopathy. Lasers Surg Med. 2008; 40:671-675.
  37. Ruiz-Moreno JM, Lugo FL, Armadá F, et al. Photodynamic therapy for chronic central serous chorioretinopathy. Acta Ophthalmol. 2009 Nov 27. [Epub ahead of print]
  38. Moon JW, Yu HG, Kim TW, et al. Prognostic factors related to photodynamic therapy for central serous chorioretinopathy. Graefes Arch Clin Exp Ophthalmol. 2009;247:1315-1323.
  39. Reibaldi M, Boscia F, Avitabile T, et al. Low-fluence photodynamic therapy in longstanding chronic central serous chorioretinopathy with foveal and gravitational atrophy. Eur J Ophthalmol. 2009;19:154-158.
  40. Reibaldi M, Cardascia N, Longo A, et al. Standard-fluence versus low-fluence photodynamic therapy in chronic central serous chorioretinopathy: a nonrandomized clinical trial. Am J Ophthalmol. 2010;149:307-315.
  41. Lee P Y, Kim KS, Lee WK. Severe choroidal ischemia following photodynamic therapy for pigment epithelial detachment and chronic central serous chorioretinopathy. Jpn J Ophthalmol. 2009;53:52-56.
  42. Kim SW, Oh J, Oh IK, et al. Retinal pigment epithelial tear after half fluence PDT for serous pigment epithelial detachment in central serous chorioretinopathy. Ophthalmic Surg Lasers Imaging. 2009;40:300-303.
  43. Torres-Soriano ME, García-Aguirre G, Kon-Jara V, et al. A pilot study of intravitreal bevacizumab for the treatment of central serous chorioretinopathy [case reports]. Graefes Arch Clin Exp Ophthalmol. 2008;246:1235-1239.
  44. Lim SJ, Roh MI, Kwon OW. Intravitreal bevacizumab injection for central serous chorioretinopathy. Retina. 2010;30:100-106.
  45. Seong HK, Bae JH, Kim ES, et al. Intravitreal bevacizumab to treat acute central serous chorioretinopathy: short-term effect. Ophthalmologica. 2009;223:343-347.
  46. Schaal KB, Hoeh AE, Scheuerle A, et al. Intravitreal bevacizumab for treatment of chronic central serous chorioretinopathy. Eur J Ophthalmol. 2009;19:613-617.
  47. Kloos P, Laube I, Thoelen A. Obstructive sleep apnea in patients with central serous chorioretinopathy. Graefes Arch Clin Exp Ophthalmol. 2008;246:1225-1228.
  48. Jain AK, Kaines A, Schwartz S. Bilateral central serous chorioretinopathy resolving rapidly with treatment for obstructive sleep apnea. Graefes Arch Clin Exp Ophthalmol. 2010 Jan 5. [Epub ahead of print]
  49. Golshahi A, Klingmüller D, Holz FG, et al. Ketoconazole in the treatment of central serous chorioretinopathy: a pilot study. Acta Ophthalmol. 2009 May 12. [Epub ahead of print]
  50. Nielsen JS, Bachhawat A, Jampol LM. A case of chronic severe central serous chorioretinopathy responding to oral mifepristone: update. Retina. 2008; 28:1363.
  51. Caccavale A, Imparato M, Romanazzi F, et al. A new strategy of treatment with low-dosage acetyl salicylic acid in patients affected by central serous chorioretinopathy. Med Hypotheses. 2009;73:435-437.

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