Synchysis scintillans

Synchysis scintillans is a degenerative condition of the eye resulting in liquefied vitreous humor and the accumulation of cholesterol crystals within the vitreous. It is also known as cholesterolosis bulbi. The vitreous liquifies in a process known as syneresis. Synchysis scintillans appears as small white floaters that freely move in the posterior part of the eye, giving a snow globe effect. It is most commonly seen in eyes that have suffered from a degenerative disease and are end-stage.^[1]

The condition is seen rarely. Associated with the advanced stages of diabetic retinopathy, but the exact pathogenesis is unknown.

The condition is symptomless and untreatable. In ophthalmoscopic examination it appears as small, flat, yellow, highly refractive crystals of cholesterol floating freely in the vitreous. These will settle, due to gravity, if the eye is immobilized.

The earliest known description of synchysis scintillans was recorded in 1828 by French ophthalmologist Jean-Francois Parfait-Landrau.^[2] He described the condition as brilliant gold-colored powder-like particles within the vitreous humor of the posterior chamber of the human eye.^[2][3][4][5]

In 1831, german-austrian ophthalmologist Johann Adam Schmidt found that these particles could migrate towards the anterior chamber of the eye, noting a "shower of silver- and gold dust" released when he opened the anterior chamber of a blind eye.^[4]

Several cases and research of synchysis scintillans had been made since then, found both in posterior chamber and anterior chamber of the eye. It had long been postulated that the particles were made of cholesterol crystals, given its resemblance under light microscopy. In 1963, Kumar determined that these crystals were composed of cholesterol through chemical analysis.^[4]

Epidemiologic studies on synchysis scintillans are limited, and the condition is considered rare. It is estimated to have a prevalence of approximately 0.003% and affects men and women equally.^[6]

Historically, synchysis scintillans has been described as occurring in relatively younger adults, most commonly reported in the third decade of life, and typically affecting both eyes, with unilateral disease considered uncommon.^[7] However, more recent case reports and clinical series have demonstrated that the condition may also occur in older adults, particularly in the seventh decade of life, and that unilateral involvement may be more common than previously thought.^[6] Reported cases have occurred across a wide age range, with the youngest reported patient at approximately 1.5 years of age and the oldest at 83 years.^[8][9]

Synchysis scintillans has historically been associated with severely damaged or chronically diseased eyes.^[5][7][10] It has been linked most frequently to long-standing vitreous hemorrhage and chronic retinal detachment.^[7][10][11] Additional reported associations include the following:

• ocular trauma^[10]
• chronic intraocular inflammation ^[7][12]
• hyphema^[7]
• secondary glaucoma^[7][13]

The condition has also been reported in association with several retinal or intraocular diseases, including:

• Coats disease^[5]
• Eales disease^[9]
• Retinoblastoma^[14]
• retinal vascular disorders, such as retinal capillary hemangioma.^[15]

Although classically described in diseased eyes, synchysis scintillans has also been reported as an incidental finding in eyes without severe ocular pathology. It has been reported to occur in patients with no or only mild ocular disease, and associations with conditions such as cataract were noted. These observations have led some authors to suggest that synchysis scintillans may occasionally represent a degenerative change related to aging of the vitreous rather than exclusively a consequence of severe ocular damage.^[6]

The pathophysiology of synchysis scintillans is not completely understood, but several mechanisms have been proposed.

One widely accepted proposed mechanism involves the breakdown of intraocular red blood cell products. The lipid rich-cell membrane releases intraocular cholesterol during degradation, creating a lipid-rich environment that favors cholesterol crystallization.^{[7][13][16][17][18][19]} This mechanism is thought to occur in chronic vitreous hemorrhages or hyphemas.^[18] Repeated hemorrhages, impaired vitreous blood absroption, or retinal neovasculrization may further promote crystal formation. ^[7][13][19]

Cholesterol crystals can also arise independently of hemorrhage in the setting of degenerative ocular conditions.^[18][13] Chronic retinal detachment is an implicated source of crystals. The lipid-rich subretinal fluid may pass through retinal defects or degenerative retinal tissue into the vitreous cavity, where cholesterol then crystallizes. ^{[5][17][18][16][10][19]}

Changes in the ocular barrier systems and intraocular fluid composition may contribute to crystal formation.^[17] Trauma, inflammation, or degenerative disease can disrupt the blood-aqueous of blood-retinal barriers, allowing cholesterol, serum lipids, and red blood cells to enter intraocular structures.^[17] This facilitates a lipid rich environment and subsequent crystal fromation. Degenerative vitreous changes may impair the ability to maintain normal levels of cholesterol within the intraocular vitreous solution, allowing precipitation of crystals.^[13][18] Fluid composition can also be compromised in the setting of a blood absorption insufficiency. ^[13]

Biochemical changes within the vitreous fluid may play a role in crystal formation. Vitreous fluid analysis from affected eyes showed evidence of oxidative stress and lipoperoxidation. The vitreous environment had reduced antioxidant enzyme activity and increased oxidative lipid by-products. Lipid oxidative damage may contribute to cholesterol crystalization.^[20]

Although synchysis scintillans primarily involves the vitreous cavity, cholesterol crystals have been rarely reported in the anterior chamber.^{[17][5][7][13]} Several mechanisms have been proposed. Crystals may form in situ following anterior chamber hemorrhage or hyphema, but more commonly form in the posterior segment and then migrate anteriorly.^[17][5][7] Structural changes that facilitate this migration include aphakia, pseudophakia, lens subluxation or luxation, zonular degeneration, or iris atrophy that create abnormal communication between ocular structures. ^{[10][17][19][5][7][18]}