Author: Ameen Marashi, MD

History

Documentation of age, type A personality, psychogenic stress, and visual loss is essential, which includes blurred vision, micropsia, metamorphopsia, scotoma, color saturation [1], and duration along with detailed ocular history.

Medical history is obtained to rule out systemic steroid use such as oral, intravenous, or local applications such as topical dermal or inhaled [2].

It is essential to rule out a history of kidney or heart transplantation [3] or other diseases that may increase the risk of endogenous cortisol production, such as Cushing disease.

Any systemic disease such as hypertension, sleep apnea [4], allergic respiratory diseases, alcohol, smoking [5], gastroesophageal reflux or Helicobacter pylori infection [6] should be documented due to association with CSCR.

Pregnancy is a high risk for developing CSCR, especially in the third trimester, which resolves by itself after delivery [7].

Ocular Examination

A list of ocular examination should set

1) Best-corrected visual acuity (BCVA) for near and far is an essential step that can perform by a trained optometrist or certified ophthalmologist to document the visual impairment as a hyperopic shift in refraction is noticed due to anteriorly displaced neurosensory retina, and the hyperopic correction may improve patients vision.

2) A slit-lamp examination done with a thorough exam of clarity and regularity of the cornea and conjunctival abnormality such injection of conjunctival vessels should be documented, and any other inflammations of the conjunctiva or eyelids documented, along with iris

exam and crystalline lens exam to rule out cataract or intraocular lens (IOL) to document the position and clarity of the posterior capsule.

3) Intra Ocular Pressure (IOP) documentation is essential as high IOP is associated with a patient with glaucoma history.

Note when high IOP spotted a corrected IOP documented after central corneal thickness measurement.

4) Bilateral dilated fundus exam is an essential and detailed examination of the optic disc (to rule out optic disc pit), macula, posterior pole, a mid-peripheral and peripheral retinal exam with specialized indirect wide-field lenses using slit-lamp biomicroscopy or indirect ophthalmoscopy to document the following:

· In acute cases, a well-demarcated oval shape or round neurosensory retinal detachment usually at the center of the posterior pole and sometimes noncentral.

· One or multiple serous small pigment epithelial detachments.

· Yellow dots may sometimes appear as a result of phagocytosed photoreceptors.

· RPE atrophic or granular changes in chronic cases.

· Subretinal fibrin leads to a reduction in vision.

· Cystic macular edema with subretinal exudation can be a sign of subretinal choroidal neovascularization.

Diagnostic tests

Fundus images

Fundus image for CSCR may show neurosensory detachment with or without yellow dots on the posterior surface of the neurosensory detached retina may be associated pigment epithelial detachment and may show irregular, atrophic pigmentary defects at the level of the RPE exhibiting granular formation in chronic CSCR. Some of the cases may present with subretinal fibrosis or exudation, especially with those complicated with CNVm.

However, multimodal imaging may provide more information about macular changes in CSCR than simple fundus images.

Fundus image may not play a critical role in managing and diagnosing CSCR but may show some clue of retinal changes during follow up and treatment such as resolved subretinal fluids or changes to RPE.

Optical Coherence Tomography (OCT)

OCT is a necessary ancillary test to diagnose patients with CSCR, which shows the following characteristics:

· Increased choroidal thickness bilaterally even in cases of unilateral CSCR [8] .

· Dilated Haller’s with compressed Sattler's layer, choroidal changes are best observed using SS-OCT or EDI (enhanced depth imaging) SD-OCT.

· RPE can show detachments with visible Bruch’s membrane forming a double-layered sign. In chronic cases, RPE may show granular changes and sometimes atrophy [9]. However, flat irregular PED may indicate the presence of CNVm which should be confirmed with OCTa [34].

· Subretinal fluids are one of the most important features of the CSCR on OCT; it appears as a hyporeflective neurosensory detachment where OCT may accurately locate the neurosensory detachment.

· In cases complicated with CNVm, there would be a fibrovascular PED presents occult CNVm.

· Outer retinal layers may show elongation of outer photoreceptor segments in the area of neurosensory detachment, in chronic cases there would be changes in outer retinal tissues that explain the reduction of vision despite regressed subretinal fluids, sometimes erosion of these segments can be found indicating an active leak from RPE and floating parts of them can be located within the subretinal fluids [10] .

· Hyperreflective dots can be a sign of remodeling of chorioretinal structures and associated increased subfoveal choroidal thickness and central macular thickness [11] , where an increasing number of hyperreflective dots may be associated with worse visual prognosis [12] .

· In cases complicated with CNVm, there would be retinal cystic formation and increased central retinal thickening; however, chronic cases may exhibit similar cystic changes but due to retinal degenerative process causing intraretinal cavitation.

· Disruption of the ellipsoid zone is the prognosis of poor visual outcome.

. The presence of subretinal fluid in the retina should be distinguished from other diseases such as a dome-shaped macula, a staphyloma, acquired vitelliform lesions, or a tumor, inflammation (VKH, posterior scleritis, etc.), drug toxicity, vascular disease of the retina, optic pit maculopathy, CNV, or systemic disease (hypertension during pregnancy, hypertensive retinopathy).

OCT is important to assess treatment efficacy for CSCR or progression post follow up as regressed CSCR has the following features:

· Reduced choroidal thickness [13].

· Resolved subretinal fluids and neurosensory detachment.

OCT angiography

In cases of non-neovascular CSCR, OCTa in the outer retinal slab may show a well-circumscribed area of no vascular flow presenting an area of pigment epithelial detachment due to shadowing artifact and sometimes may show choriocapillaris due to misalignment of outer segment line.

In cases of neovascular CSCR, OCTa can clearly show the occult choroidal neovascularization in the outer retinal slab, which can be well-circumscribed in the form of lacy or sea fan-shaped or poor circumscribed and sometimes the CNVm can be seen in all retinal layers slab.

OCTa is essential to diagnose CSCR cases complicated with CNVm, especially when it is hard to confirm the diagnosis with OCT, or FFA.

OCTa can be very useful to follow up CNVm regression post intravitreal injection of Anti-VEGF.

Fluorescein Fundus Angiography (FFA)

FFA has unique characteristics in diagnosing CSCR such as:

· The early leak in the form of inkblot starts as a pinpoint and increases with mid and later phases or smokestack, which appears as ascending leakage in early phases and exhibits the form of umbrella or mushroom in late phases [14] .

· Pigment epithelial detachment may show hyperfluorescence in early stages, increasing in intensity and shows sub RPE dye pooling in late stages.

· Subretinal fluids may show subretinal dye pooling and may show hyperfluorescence in mid phases.

· In chronic cases, a granular hyperfluorescence with leak sometimes may show intraretinal leakage due to intraretinal cystic changes.

· Cases complicated with CNVm show stippled hyperfluorescence and pooling, it may show circumscribed hyperfluorescence with leakage simulating subretinal CNVm.

FFA is very useful to determine the leakage source when planning to treat CSCR using laser or PDT.FFA can help to differentiate CSCR from other diseases such as Harada.

Note that the physician should obtain signed consent explaining the rare complications of FFA, including death 1/200000, and FFA facility should have an emergency plan in situ.

Indocyanine green angiography (ICGA)

ICG is an important tool to study the pathology of CSCR, and as a guide for PDT application, ICG show the following characteristics:

· Early phase shows lobular hypoperfusion

· Mid phase shows multiple areas of hyperfluorescence in the inner choroid

· In the late phase, venous congestion in the form of outlined larger

choroidal vessels wherein chronic cases a blockage or subretinal staining due to subretinal deposits.

· CNVm may show staining in the late phases of ICG.

Fundus Autofluorescence (FAF)

FAF shows increased autofluorescence areas at the area of serous retinal detachment, especially at its borders. In acute cases, small spots of increased autofluorescence are correlated to precipitates located in the subretinal space seen on fundus images or clinical examination. FAF shows in chronic cases hypo autofluorescence in areas of subretinal fluids [15], and PEDs as subretinal fluids resolved a hyper autofluorescence increases due to the accumulation of fluorophores as in it may exhibit gravitational track in the form hypo autofluorescence surrounded with hyper autofluorescence [16].

Managing patients with CSCR

Treatment options

Anti-corticosteroid therapy

May improve subretinal fluid and improve BCVA in chronic cases of CSCR, [17] such as non-selective mineralocorticoid antagonists spironolactone 25mg or 50 mg daily.

When ordering mineralocorticoid antagonists, the potassium levels and creatinine levels should be monitored especially in patients with congestive heart failure and chronic kidney disease especially when serum potassium levels are > 5.5 mEq/L and serum creatinine >2 mg/dl in men and >1.8 mg/dl in women [18].

Another anti-corticoid therapy is rifampin 300 mg b.i.d. which increases the metabolism of steroids and shows to improve CSCR, but it should be avoided in countries with a high prevalence of tuberculosis to reduce the risk of resistance [19].

Other systemic therapies

Aspirin: a low dose of 100 mg for one month then 100 mg for the alternating day for five months showed improvement

of subretinal fluids and improved vision in CSCR patients [20].

Helicobacter pylori treatment: patients with CSCR tested positive with Helicobacter pylori showed improvement of CSCR when treated with both metronidazole and amoxicillin 500 mg t i.d. for two weeks and omeprazole once for six weeks [21].

Carbonic Anhydrase Inhibitors: Acetazolamide may provide rapid subjective improvement of vision but didn’t reduce the recurrence rate nor change final visual acuity [22].

Photodynamic therapy (PDT)

PDT can reduce the choroidal vascular hyperpermeability, and choroidal thickness along that successful PDT treatment may reduce the risk of recurrences.

Half dose PDT is as effective as regular PDT [23] with fewer complications such as the risk of RPE atrophy, choroidal ischemia, and visual loss, subretinal scar, and CNVm formation and half-dose PDT are more effective than half fluence PDT [24] for treatment of CSCR the technique is by applying 3 mg/m2 of verteporfin with 10 minutes of infusion. After 5 minutes, an ICG guided photodynamic therapy applied using 689nm for 83 seconds delivering energy of 50 J/cm2 by the intensity of 600 mW/cm2 and spot size 1000 μm. To achive a half fluence PDT then use 25 J/cm² of light at 300 mW/cm²

Subthreshold microsecond laser

Subthreshold microsecond laser is a safe method to treat central and non-central cases without inducing retinal scars or scotomas by stimulating RPE function with down regulating cytokines production and inflammations [25].

Low-intensity high-density protocol with spot size 100-200 μm with duration 0.2s.

Power adjusted (on the non-edematous nasal retina) using the titration method with a 5 % duty cycle, the power used in treatment is half of the power used to achieve tissue reaction using a microsecond laser with 5% duty cycle.

Subthreshold microsecond laser can be ICG guided or applied on the area of the leakage as identified by FFA; also, subthreshold microsecond laser can be applied to the area of subretinal fluids.

Laser Photocoagulation

Treatment of laser is widely abandoned by retinal physicians around the world due to complications such as visual threatening scar formation [26] and maybe only utilized for non-central cases far enough that post-laser scar formation won’t cause visual loss or threatens the foveal avascular zone.

VEGF Blockade agents

Is only indicated when CSCR is complicated with CNVm [27] ; otherwise, there is no proof that VEGF blockade agents are indicated to treat non- neovascular CSCR.

Treatment plan

In cases of acute CSCR presented for less than three months

- Observation recommended for three months as most cases will resolve spontaneously [28]; however, the treatment recommended only in individuals with high visual demands, recurrent CSCR, or other eye suffered from poor visual outcome post-CSCR [29].

- Adjusting systemic factors such as stopping steroid use, psychological therapy, and managing sleep apnea [30].

In cases of chronic CSCR presented for more than three months

- Half dose PDT recommended [31]; however, in the absence of PDT, treatment with subthreshold microsecond laser is considered [25].

- OCT repeated after two months to assess treatment efficacy.

- Treatment with laser photocoagulation considered in non-central CSCR.

In cases of non-resolving subretinal fluids or recurrent CSCR

- PDT or subthreshold laser can be repeated in recurrent cases. However, a cross over from subthreshold laser to PDT may have better visual and anatomical outcomes from cross-over from PDT to a subthreshold laser [35].

- Anti-corticosteroid therapy, such as spironolactone, considered in non- resolving cases of CSCR persisted for five months [17], where OCT repeated after five weeks to assess efficacy.

- In patients tested positive with Helicobacter pylori may benefit from both metronidazole and amoxicillin 500 mg t. i. d. for two weeks and omeprazole once for six weeks [21].

-Aspirin may be considered, especially in patients, who are above 40 years old [20].

- A combination of therapies can be considered in persistent cases to solo therapy.

In cases of neovascular CSCR

Intravitreal injection of VEGF blockade agents considered as a treatment of choice [27] when the presence of CNVm established using OCTa, FFA, or ICG, especially in patients with CSCR and above 50 years old [32].

Flow chart summarizes the approach and management of central serous chorioretinopathy

Follow up and prognosis

-As mentioned above CSCR may resolve spontaneously, but with recurrence rate up to 25-50% within one year, all therapies as mentioned above may not alter final visual acuity but accelerate the absorption of subretinal fluids and visual improvement; therefore, there might be some compromises in visual quality or acuity due to permanent damage to photoreceptors and outer retinal layers [33].

- Patients suffering from multiple episodes of disease recurrence, multiple areas of subretinal fluids, and prolonged course of disease tend to have a worse prognosis.

- The best way to follow up CSCR changes is by OCT; however, patients can use the Amsler grid to do self-monitoring for new symptoms.

-The Fuji sign is seen in 42% of chronic CSCR patients with spontaneous resolution, versus 13% of controls. In addition, there are fewer focal FA leakage points at baseline in chronic CSCR patients with spontaneous resolution.

Add your scientific contribution

These guidelines were reviewed and updated in December 2022