Choroidal Folds

Etiology

Broadly, the conditions associated with choroidal folds are:[4]

• Idiopathic- Previously, it was thought to comprise most of the cases of choroidal folds. However, with recent investigations, it is noted that a cause can be found in up to 85% of cases with a thorough work-up.[5][6] Pathogenesis is unknown but may be traced to some inflammation in the posterior sclera in the late prenatal stage or during childhood without any clinical findings at that time, which leads to shrinkage of the sclera.
• Reduced intraocular pressure (hypotony): This occurs due to volume loss as a result of loss of lens, aqueous or vitreous humor, which is combined with an opening in the globe. The common causes are:
• After ocular surgery (including cataract or glaucoma surgery)
• Cyclodialysis
• Trauma
• Compression/distortion of the globe/choroid/ocular coats: In these cases, choroidal folds occur due to mechanical displacement of surrounding choroid in cases of choroidal tumors or increased pressure on the globe with traction on the optic nerve due to an orbital mass.
• Increased orbital tissue/orbitopathy- Edema and congestion within the orbit, combined with the enlargement of extra-ocular muscles leads to choroidal folds, especially in Graves’ ophthalmopathy.[7][8]
• Orbital inflammation- idiopathic orbital inflammatory disease
• Orbital infection due to chronic sinusitis and orbital cellulitis.[9] In such cases, choroidal folds may be caused by scleral shrinkage because of mild, chronic, or periocular inflammation.
• Scleral buckling procedure- Encircling element reduces the circumference of the globe under the buckle but also stretches sclera and choroid in a direction perpendicular to it, thus leading to choroidal folds perpendicular to the plane of the buckle.[8]
• Orbital mass including cavernous hemangioma, optic nerve meningioma, hemangiopericytoma, lymphoproliferative lesion, dermoid, mucocele, and metastatic neoplasms lead to increased pressure on the globe with traction on the optic nerve which perpetuates choroidal folds.
• Retrobulbar injection/anesthesia
• Choroidal tumors such as melanoma, nevus, and metastasis produce choroidal folds due to the mechanical displacement of the surrounding choroid.
• Choroidal detachment- compressive forces at the edge of choroidal detachment push the choroidal tissue aside, leading to the formation of choroidal folds locally.
• Increased choroidal thickness/thickness of ocular coats in eyes that might have a short axial length: Choroidal folds develop in these conditions due to an increase in either choroidal volume due to congestion or thickness which throws it into folds.
• Uveal effusion syndrome[10][11]
• Central serous chorioretinopathy (CSCR)[12]
• Nanophthalmos [13]
• Choroidal effusion
• Hypermetropia[14]- Along with congestive choroidal thickening, scleral shortening and redundant Bruch’s membrane also contribute to choroidal fold formation.
• Optic nerve disorders: swelling of the optic nerve head compresses the peripapillary choroid throwing it into folds.
• Papilloedema
• Pseudopapilledema[15]- Optic disc drusen, Alagille syndrome
• Increased intracranial tension: may cause choroidal folds even though clinically papilledema may not be evident[5][6]
• Ocular inflammation
• Posterior scleritis[16]
• Vogt-Koyanagi-Harada (VKH) disease[17]
• Sympathetic ophthalmia
• Other causes
• Choroidal neovascularization and scar-due to contraction of sub-retinal pigment epithelium neovascular complex in cases of neovascularization.[17][18]
• After spontaneous resolution of a dural cavernous sinus fistula[17]
• Space flight-associated neuro-ocular syndrome (SANS): Cephalad fluid shift causes venous congestion in the head and neck that leads to increased vortex venous pressure, which in turn causes blood stagnation in the choroid causing its expansion and choroidal fold formation. Also, globe flattening and disc edema occur due to raised intracranial tension being transmitted through the optic nerve to the optic disc.[19][20]
• Acquired hyperopia with choroidal folds[21]
• Diode endolaser photocoagulation of the retina[22]

The suggested etiologies depend on associated conditions and are as follows:[4]

• Thickening of choroid by congestion in the choriocapillaris in cases of hypotony or choroidal tumors
• Deformation of the sclera due to optic nerve traction as in cases of orbital masses, and hypotony
• Thickening or shrinkage of sclera due to chronic traction or chronic inflammation
• Decreased scleral rigidity, especially in young myopes because of the elongated eyeball and thin sclera[1]
• Contraction of the sub-retinal pigment epithelium choroidal neovascular complex in cases of neovascularization[18]

The characteristic striations seen in the case of choroidal folds are thought to be due to choriocapillaris congestion along with its attachment to overlying Bruch’s membrane.[3] In the absence of these attachments and congestion of the choriocapillaris, the retinal pigment epithelium can slip over the choriocapillaris. This will prevent choroidal fold formation.

Epidemiology

There are no prevalence figures available on the occurrence of choroidal folds in the general population.[4]

History and Physical

Patients may be asymptomatic or may complain of worsened visual acuity or metamorphopsia.[1] Patients may be asymptomatic when mild choroidal folds develop. Visual dysfunction is more common in acutely developed choroidal folds. Patients with long-standing folds usually have normal visual acuity.

On ocular examination, choroidal folds are visualized, which are best appreciated with a slit lamp and +90D or +78D lens. A red-free filter accentuates the appearance of folds.

Other relevant ocular and systemic history, according to the associated condition may be present.

In cases of idiopathic choroidal folds, the most common type, patients are invariably asymptomatic males that present with presbyopia. These cases usually have hyperopia. The choroidal folds can be either bilaterally symmetrical or occur in one eye, followed by the involvement of another eye during the observation period. The folds are usually bilaterally symmetrical, parallel, and confined to an area above and below the optic disc and macula.[18] Such cases may represent uveal effusion syndrome, previous episode of posterior scleritis, and increased intracranial tension, therefore all possible causes must be excluded before labeling a case as 'idiopathic'.

Cases of acquired hyperopia with choroidal folds are usually in males and are detected on routine examination or with a complaint of blurred vision. Along with choroidal folds, they may be associated with ophthalmic findings such as mild disc swelling, focal retinal pigment epithelial defects, phoria or tropia, and central serous pigment epitheliopathy.[21]

In the case of choroidal tumors, the choroidal folds surround the tumor base. Since the tumor stretches the overlying choroid, there are no folds above the choroidal tumor.

The intraocular pressure is usually less than 6 mm of Hg in choroidal folds related to hypotony. The choroidal folds are broad and randomly oriented.[23] Other signs of hypotony include tortuous and engorged retinal vessels, stellate folds around the center of the fovea, and rarely cystoid macular edema.

In the case of nanophthalmos, patients have small hyperopic eyes which are in a deep orbit with narrow palpebral fissure. Other features include an elevated papillomacular bundle, retinal fold, pigmentary retinopathy, and macular holes.[24]

Cases of papilledema usually present with symptoms of headache, nausea, vomiting, and sometimes with associated transient visual obscurations. The fundus examination usually shows papilledema and choroidal folds concentric to the disc along with horizontal choroidal folds over the macula, which converge towards the nasal margin of the optic disc.[25]

A scleral buckle is usually placed in cases of rhegmatogenous retinal detachment. Choroidal folds in such cases are usually formed near the posterior slope of the buckle.

Cases of uveal effusion have a waxing and waning clinical course. The choroidal folds are associated with serous choroidal detachment. Sometimes these cases would just have choroidal folds as the initial sign.[11] Other associated features include dilated episcleral vessels, presence of few vitreous cells, intraocular pressure within the normal range, retinal pigment epithelial changes, and exudative retinal detachment with shifting fluid.

Cases of posterior scleritis present with a unilateral decrease in vision with severe pain (may not allow the patient to sleep or may awaken the patient from sleep), mild proptosis, and restricted ocular movements with pain during ocular movements. These patients may have a history of rheumatoid arthritis, collagen vascular diseases, or other autoimmune diseases. The ocular examination usually reveals a localized choroidal elevation, which is surrounded by concentric choroidal folds.[16]

VKH disease usually has a clinical course passing through the following stages: prodromal phase, acute uveitic phase, convalescent phase, and chronic recurrent phase. The prodromal phase manifests as tinnitus, ocular pain, low-grade fever, photophobia, and nuchal rigidity. The acute uveitic phase manifests as a visual loss with fundus findings of choroidal folds, exudative retinal detachment, disc edema, and Dalen-Fuchs nodules.[17][26] The acute uveitic phase is followed by the convalescent phase, which itself manifests as alopecia, poliosis, and vitiligo with depigmentation of choroid giving a ‘sunset glow fundus’. The chronic recurrent phase is characterized by cataracts, glaucoma, or choroidal neovascularisation.

SANS is seen in astronauts who usually present with hyperopic refractive error, disc edema, choroidal folds, and retinal cotton-wool spots after long-duration space travel.[27]

In the case of intra-conal lesions, patients usually have hyperopia, whereas extra-conal lesions lead to astigmatism. In cases of orbital lesions, a choroidal fold pattern gives us a clue to localize the lesion.

Choroidal folds have a variable pattern depending on whether the orbital lesions are intra-conal or extra-conal.

• In intra-conal lesions, choroidal folds are produced as a result of the expansion of tumors between the muscle cone and optic nerve. If the lesion pushes the optic nerve to one side, the choroid is compressed in the direction where the nerve is pushed and comes under tension in the opposite direction resulting in a parabolic fold pattern with the optic nerve head in between the folds.
• Extra-conal lesions, being located between the orbital wall and muscle, do not directly compress the optic nerve. In such cases, choroidal folds are usually concentric and perpendicular to the direction of the compressive force of the lesion.[28]

Evaluation

Fundus fluorescein angiography (FFA) demonstrates more severe fundus changes than routine slit-lamp examination. After fluorescein injection, the peaks fluoresce, and the troughs remain dark. The peaks and troughs can be better contrasted during the subsequent arterial and venous phases when they appear as alternating bright and dark lines, but there is no leakage.[29][30] More folds are detected on fluorescein angiography as compared to light ophthalmoscopy.[4]

FFA in cases of VKH disease shows pinpoints of hyperfluorescence, which in later stages of disease show pooling surrounded by a dark rim.[31]

CSCR shows leakage in a characteristic inkblot or smokestack or diffuse leak pattern on FFA.

FFA in choroidal metastasis helps in assessing the size of the lesion and identifying flat lesions of choroidal invasion, which would have been missed on clinical examination. They are hyperfluorescent in the early phase, which becomes hyperfluorescent in the late phase. The tumor border shows dilated retinal capillaries with pinpoint leakage in many cases.[32]

Indocyanine green angiography (ICGA) may help to examine the choroidal conditions associated with choroidal folds. VKH disease in its acute phase shows hyperfluorescent dark dots, early hyperfluorescent choroidal stromal vessels, and fuzzy stromal vessels. Central serous chorioretinopathy (CSCR) shows delayed choroidal filling along with hyperfluorescent areas in the early phase, choroidal hyperpermeability leading to geographic areas of hyperfluorescence in mid-phase with persistent hyperfluorescence or washout in the late phase.[33] Mid and late phases in the active cases of CSCR are associated with punctate hyperfluorescence.[34]

Ultrasound B scan (USG) is a non-invasive technique that does not detect choroidal folds but demonstrates flattening and thickening of the posterior sclera and choroid.[35][36] It provides characteristic images in cases of choroidal mass, retrobulbar mass, posterior scleritis, and other conditions.[1] It also helps in determining axial length to diagnose nanophthalmos.[13] It can measure the choroidal thickness and the flattening of the posterior pole in cases of orbital mass.

USG is a very important tool in the diagnosis of posterior scleritis in which posterior coats of the eye appear thickened and flattened. Other common findings are retrobulbar edema, ‘T’ sign if the retrobulbar edema surrounds the optic nerve, retinal detachment, distension of optic nerve sheath, optic disc swelling, and scleral nodules.[37][38]

Optical coherence tomography (OCT) shows the presence of undulating retinal pigment epithelium in cases of choroidal folds.[39] Associated OCT findings in CSCR include neurosensory detachment, usually with pigment epithelial detachment.[40] VKH shows characteristic multilobular outer retinal/subretinal serous exudates pooling with septa, which are considered to be highly diagnostic.[41]

OCT angiography may help to find out the role of abnormal blood flow in the pathophysiology of choroidal folds.[1]

Blood pressure should be measured in all cases of papilledema to rule out accelerated hypertension.

Radiological investigations like CT scans and MRIs may often be necessary to investigate an underlying condition. For example, idiopathic intracranial hypertension in cases of acquired hyperopia where variable enlargement of the optic nerve image, flattening of the posterior pole of affected eyes, and sometimes a discernible space between the nerve and its sheath is seen.[21][42]

Invasive procedures like lumbar puncture may be required in selected cases. Uveal effusion may show an increase in the cerebrospinal fluid (CSF) protein level and increased CSF pressure without pleocytosis.[10] VKH may show CSF pleocytosis in the prodromal stage. Some authorities recommend that lumbar puncture should be performed before labeling a case as idiopathic, especially if imaging is unremarkable to rule to high intracranial pressure.[5][6]

Since choroidal folds can be associated with thyroid orbitopathy, thyroid function tests can be done in suspected cases.[43]

Treatment / Management

Unilateral cases of choroidal folds have a higher chance of orbital disease and more severe ocular disease than bilateral presentations.[44] Management should be directed towards treating the underlying cause. The diagnosis of the underlying pathologic situations leading to choroidal folds can become challenging. A proper tailored approach taking into consideration the specific features of each case is necessary so that potentially serious and treatable conditions are diagnosed with optimal investigations.[1](B2)

Idiopathic cases can be observed as they are usually asymptomatic. Cases of acquired hyperopia with choroidal folds can usually be observed as no active treatment is required. Management of choroidal tumors varies depending on the suspected tumor.

Observation with lifestyle modification is usually the first line of treatment in most cases of CSCR. Chronic or recurrent cases can be treated with argon laser or green 532 nm frequency-doubled Nd-YAG laser photocoagulation, or micropulse diode laser to point of leakage. Photodynamic therapy is another modality. Carbonic anhydrase inhibitors and anti-corticosteroid therapy have also been tried with variable results.[45][46]

Cases of severe uveal effusion can be treated with scleral flaps excision and decompression of vortex veins.[11] Nanophthalmic or smaller eyes have a high risk of developing complications like uveal effusion and angle-closure glaucoma.[47] Management in such cases should be directed towards treating the complications. Angle-closure glaucoma can be treated with laser iridotomy, trabeculectomy, or pars plana lensectomy with vitrectomy.[48](B2)

Cases of papilledema should be evaluated for causes of raised intracranial tension and managed accordingly.

Management in cases of hypotony should be directed to find out the underlying cause. Posterior scleritis cases can be started with oral analgesics and corticosteroids. Refractory cases can be given intravenous corticosteroids. High-dose systemic corticosteroids and immunomodulatory therapy are important in the management of VKH disease. Cases of active choroidal neovascularization are treated with anti-VEGF (vascular endothelial growth factor) agents. Choroidal scars may be observed. Cases of space flight-associated neuro-ocular syndrome should be managed similarly to papilledema. Space anticipation glasses can be used to counteract the hyperopic shift on the International Space Station. Acetazolamide and venoconstrictor thigh cuffs to counteract cephalad shift of fluid and lower body negative pressure techniques have also been tried.[20] Management of cases with orbital lesions should be done as per the identified lesion. Management of orbital cellulitis and chronic sinusitis centers around treating these conditions with broad-spectrum antibiotics for at least 2 to 3 weeks.[49](B3)

Management of Graves ophthalmopathy requires a multidisciplinary approach of both endocrinologists and ophthalmologists. Though converting the patient to a euthyroid state is important, it is not necessary if ophthalmic complaints require urgent treatment. Hyperthyroidism can be treated with anti-thyroid drugs, radioactive iodine, or thyroidectomy. Graves’ ophthalmopathy can be treated with supportive measures like lubricants and smoking cessation. Corticosteroids and radiation therapy can also be tried. Surgery may be done for orbital decompression, strabismus, and eyelid retraction.[50]

Differential Diagnosis

Retinal folds which can accompany choroidal folds are important in the differential diagnosis. Retinal folds usually have a normal fluorescein pattern. Retinal folds are usually narrower than choroidal folds, and they seem to radiate from pathological lesions in the retina. There is usually an abnormal vitreous or vitreoretinal interface associated with it. They may show increased tortuosity of retinal blood vessels. Retinal folds may occur with an epiretinal membrane, subretinal scar, subretinal neovascular membrane, subretinal fluid, uveal or scleral thickening, or with optic nerve disease.[4][44] Retinal pigment epithelial folds commonly occur with choroidal folds and are found in cases of macular degeneration and appear as fine pigmentation lines alternating with light orange. They look like thick, wrinkled cloth on slit-lamp biomicroscopy. It is specifically associated with pigment epithelial detachment and subretinal neovascularization.[44]

Staging

Chorioretinal folds can lead to maculopathy which has been staged with the help of FFA into:[51]

• Stage 1: Alternating bands of hyperfluorescence and hypofluorescence without any staining or leakage
• Stage 2: Areas of staining at the crest of the folds
• Stage 3: Stippled hyperfluorescence expanding in the late frames

The fluorescein pattern in stage 3 is similar to the late leakage of the undetermined source described in the macular photocoagulation study.[52]

Prognosis

Prognosis in the case of choroidal folds depends upon the associated underlying conditions:

• Idiopathic choroidal folds, acquired hyperopia with choroidal folds usually have good visual acuity and good prognosis.
• Choroidal folds in association with diode endolaser photocoagulation remain stable over the long term.[22]
• Prognosis in cases of hypotony is good if detected early and treated. The choroidal folds may disappear completely if intra-ocular pressure returns to normal.
• Prognosis in cases of uveal effusion is variable with permanent loss of vision in severe cases.[10]
• In cases of posterior scleritis, visual prognosis is good if treatment is initiated early.[37]
• Prompt and aggressive treatment with steroids leads to a good visual prognosis in Vogt-Koyanagi-Harada disease.[53]
• Prognosis is usually good in cases of space flight-associated neuro-ocular syndrome.

Complications

Focal RPE defects can develop along the choroidal folds which can later be associated with choroidal neovascularisation. Hence, careful monitoring is required at regular intervals.[21]