Schwartz Syndrome (Schwartz-Matsuo Syndrome)

Key points of this disease

• Schwartz syndrome (Schwartz-Matsuo syndrome) is a rare secondary open-angle glaucoma in which intraocular pressure rises in association with rhegmatogenous retinal detachment.
• Photoreceptor outer segments shed from the detached retina block the trabecular meshwork, causing obstruction of aqueous humor outflow and elevated intraocular pressure.
• The cell-like floating particles in the anterior chamber are photoreceptor outer segments, not inflammatory cells, so corticosteroids are ineffective.
• The principle of treatment is retinal reattachment surgery, and since many cases involve peripheral tears in young patients, scleral buckling is the first choice.
• Successful retinal reattachment normalizes intraocular pressure and eliminates anterior chamber cells. Long-term use of pressure-lowering medications is rarely needed after surgery.
• It predominantly occurs in young males, often with a history of blunt trauma or atopic dermatitis.

1. What is Schwartz syndrome (Schwartz-Matsuo syndrome)?

Schwartz syndrome is a rare condition in which intraocular pressure rises in association with rhegmatogenous retinal detachment. It was first reported in 1973 by Schwartz as “rhegmatogenous retinal detachment with ocular hypertension”²⁾. Normally, in rhegmatogenous retinal detachment, the exposed retinal pigment epithelium (RPE) actively absorbs fluid, so intraocular pressure tends to decrease; however, in this syndrome, intraocular pressure rises contrary to this principle, which is characteristic.

In Schwartz’s initial report, it was described as chronic open-angle glaucoma secondary to rhegmatogenous retinal detachment, and it was speculated that aqueous outflow obstruction due to iridocyclitis was the cause²⁾. Later, in 1978, Davidorf proposed another hypothesis that pigment granules released from the retinal pigment epithelium block the trabecular meshwork⁵⁾.

In 1986, Matsuo et al. isolated and identified photoreceptor outer segments from the aqueous humor aspirate of patients meeting the criteria for this syndrome, supporting the etiology of trabecular meshwork obstruction by photoreceptor outer segments⁸⁾. In 1994, they published a detailed review in Survey of Ophthalmology⁷⁾, organizing the pathogenic mechanism in which photoreceptor outer segments pass through the retinal tear and reach the aqueous outflow pathway (trabecular meshwork), causing outflow obstruction³⁾. Based on this mechanism, the name “Schwartz-Matsuo syndrome” is now widely used.

Classification

In the Glaucoma Clinical Practice Guidelines (5th edition), this syndrome is classified as secondary open-angle glaucoma¹⁾. The mechanism of intraocular pressure elevation belongs to the category where “the main site of aqueous outflow resistance is in the trabecular meshwork,” and it is listed alongside corticosteroids, exfoliation material, amyloid, uveitis, lens material, trauma, ocular surgery, intraocular foreign bodies, intraocular tumors, and iris pigment¹⁾.

The European Glaucoma Society Guidelines (5th edition) also state in the section on glaucoma associated with vitreoretinal surgery that “the trabecular meshwork can be obstructed by cellular debris from the outer segments of the retina (Schwartz syndrome)” ⁴⁾.

Although it is sometimes referred to as “secondary angle-closure glaucoma,” the angle is actually open. The outflow obstruction occurs at the level of the trabecular meshwork, not by closure of the angle itself.

Epidemiology

The frequency of this syndrome in rhegmatogenous retinal detachment is rare, and large-scale epidemiological data are lacking. Phelps & Burton (1977) retrospectively reviewed 817 eyes with rhegmatogenous retinal detachment and reported cases with elevated intraocular pressure, but did not calculate the incidence specific to this syndrome ⁶⁾. The following clinical features have been reported.

• Predilection: More common in young males. High activity levels and susceptibility to trauma are considered contributing factors.
• Laterality: Unilateral
• History: Often a history of blunt trauma or atopic dermatitis. In patients with atopic dermatitis, the habit of eye rubbing is associated with the development of retinal detachment.
• Characteristics of retinal breaks: Small breaks are common in the far periphery, such as the ora serrata and ciliary body. Traumatic retinal dialysis is also a common pattern ¹⁰⁾.

Q Is Schwartz syndrome a type of glaucoma?

A

It is classified as secondary open-angle glaucoma. Photoreceptor outer segments shed from rhegmatogenous retinal detachment obstruct the trabecular meshwork, causing impaired aqueous outflow and elevated intraocular pressure. The Japanese Glaucoma Guidelines (5th edition) classify it as secondary open-angle glaucoma with the main resistance to aqueous outflow in the trabecular meshwork ¹⁾. However, since intraocular pressure normalizes after removal of the cause by retinal reattachment surgery, its course differs significantly from that of typical chronic glaucoma.

2. Main Symptoms and Clinical Findings

Subjective Symptoms

The subjective symptoms of this syndrome include those due to retinal detachment and those due to elevated intraocular pressure.

Symptoms associated with retinal detachment:

• Visual field defect: Scotoma or visual field loss corresponding to the area of detachment.
• Photopsia: Flashes of light at the time of retinal tear formation
• Floaters: Due to vitreous opacities and pigment dispersion
• Decreased vision: Prominent when the macula is involved in the detachment

Symptoms associated with elevated intraocular pressure:

• Eye pain: When intraocular pressure is significantly elevated
• Blurred vision: Due to corneal edema
• Headache: Ipsilateral frontal or temporal region
• Nausea and vomiting: During marked intraocular pressure elevation

In cases where retinal detachment progresses slowly or is confined to the inferior region, subjective symptoms may be minimal. Caution is needed because patients may present only with cell-like floaters in the anterior chamber and be misdiagnosed with uveitis. Particularly in young patients, the condition may progress without complaints of eye pain or vision loss. If unexplained anterior chamber cells and elevated intraocular pressure are found in a patient with a history of trauma, this syndrome should be considered in the differential diagnosis, and a thorough peripheral fundus examination should be performed.

Clinical Findings (Findings Confirmed by Physician Examination)

The characteristic clinical findings of this syndrome are shown below.

Finding	Characteristic
Angle	Open angle (not angle closure)
Anterior chamber	Relatively large cell-like floaters (photoreceptor outer segments)
Intraocular pressure	Elevated (with marked diurnal variation)
Retina	Shallow rhegmatogenous retinal detachment (often involving the vitreous base)
Retinal break	Small breaks in the far periphery, such as the ora serrata or ciliary body
Subretinal space	Forms cord-like structures over time
Lens	May be complicated by cataract or dislocation

The “cells” observed in the anterior chamber are fundamentally different from the inflammatory cells seen in uveitis. They are photoreceptor outer segments shed from the detached retina and are not accompanied by true iridocyclitis. The absence of keratic precipitates (KP) and anterior synechiae is important for differentiation. Photoreceptor outer segments are slightly larger than inflammatory leukocytes and appear as relatively large cell-like structures under slit-lamp microscopy.

The fact that anterior chamber cells do not respond to corticosteroid treatment is also an important distinguishing point from inflammatory diseases. Even with steroid eye drops or systemic administration, the anterior chamber cells do not decrease, and intraocular pressure does not improve. This “steroid-resistant” anterior chamber cell is a clue to actively suspect this syndrome rather than uveitis.

Note that the tobacco dust-like pigment (Shafer’s sign) associated with rhegmatogenous retinal detachment is a finding derived from retinal pigment epithelium and is a different phenomenon from the anterior chamber cells (photoreceptor outer segments) in this syndrome. Shafer’s sign is known as a useful finding suggesting the presence of a retinal break. Both findings may coexist in the same eye, but their origins and clinical significance differ.

Q Are the anterior chamber cells different from the inflammation of uveitis?

A

The anterior chamber cells in this syndrome are not inflammatory leukocytes or lymphocytes seen in uveitis, but rather photoreceptor outer segments shed from the detached retina. Therefore, they are not accompanied by keratic precipitates (KP), anterior synechiae, or a marked increase in flare. Furthermore, topical or systemic corticosteroid administration does not reduce the anterior chamber cells. This steroid resistance is an important distinguishing feature and directly influences treatment decisions. For details, see the section on “Diagnosis and Examination Methods”.

3. Causes and Risk Factors

Etiology

The etiology of this syndrome is that photoreceptor outer segments shed into the subretinal space due to rhegmatogenous retinal detachment pass through the retinal break along with viscous subretinal fluid, reach the anterior chamber, and obstruct the trabecular meshwork. Photoreceptor outer segments are the tips of retinal photoreceptors (rods and cones), which are normally phagocytosed and regenerated daily by the retinal pigment epithelium. When retinal detachment occurs, the normal turnover of photoreceptor outer segments is disrupted, and shed outer segments accumulate and flow into the aqueous outflow pathway. For a detailed pathophysiological mechanism, see the section on “Pathophysiology”.

Risk Factors

The following risk factors have been reported for the development of this syndrome:

• Shallow retinal detachment involving the vitreous base: Shallow detachment allows continuous shedding of degenerated photoreceptor outer segments. Additionally, involvement of the vitreous base enables outer segments to reach the anterior chamber without being blocked by the vitreous membrane.
• Retinal break or dialysis at the ora serrata: Breaks in the far periphery are close to the anterior chamber, making it easier for photoreceptor outer segments to reach the anterior chamber¹⁰⁾.
• Ocular trauma (blunt trauma): Traumatic retinal breaks or dialysis increase the risk of this syndrome⁶⁾.
• Atopic dermatitis: Patients with atopic dermatitis have a higher risk of retinal detachment and are prone to breaks near the ora serrata.
• Marfan syndrome: Due to lens subluxation and vitreous degeneration, there is a risk of retinal breaks near the ora serrata⁹⁾.
• Myopia: High myopia is a risk factor for rhegmatogenous retinal detachment, indirectly increasing the risk of this syndrome.
• Young males: In young individuals, traumatic retinal dialysis and ora serrata breaks are more frequent.

Points to Note

When elevated intraocular pressure and anterior chamber cells are observed in one eye after blunt trauma, traumatic uveitis may be diagnosed. However, if anterior chamber cells persist despite steroid treatment, the presence of peripheral retinal detachment should be suspected, and a detailed fundus examination is necessary.

4. Diagnosis and Examination Methods

Clinical Diagnostic Triad

This syndrome is clinically diagnosed by a combination of the following three clinical findings:

1. Anterior chamber cells without other signs of uveitis (the number of cells varies by case)
2. High intraocular pressure with marked fluctuations
3. Rhegmatogenous retinal detachment

Diagnosis is difficult based on anterior segment findings alone, but becomes easy once rhegmatogenous retinal detachment is confirmed.

Examination Methods

The examination methods used for diagnosis and evaluation of this syndrome are shown below. The key to diagnosis is confirmation of rhegmatogenous retinal detachment, and a multifaceted examination approach is important to avoid missing small peripheral tears.

• Dilated fundus examination: Confirmation of retinal detachment and tears. To avoid missing small tears in the far periphery (near the ora serrata), carefully observe up to the vitreous base using an indirect ophthalmoscope or a pre-corneal lens.
• Fundus examination with scleral indentation: Poor dilation or lens opacities often make tear detection difficult. Use scleral indentation to elevate the far periphery near the ora serrata and actively search for small tears. Traumatic retinal dialysis is easily missed without indentation.
• B-scan ultrasonography: Useful for confirming the presence of retinal detachment when the fundus is poorly visible due to cataract, vitreous hemorrhage, or corneal edema. Also used to estimate the extent and height of retinal detachment.
• Ultrasound biomicroscopy (UBM): Allows high-resolution evaluation of tears near the ciliary body and the anterior extent of retinal detachment. Particularly effective for detecting lesions in the pars plana, which are difficult to observe with standard fundus examination.
• Optical coherence tomography (OCT): Confirms the presence of subretinal fluid and changes in retinal layer structure. Macular OCT is also useful for preoperative evaluation of retinal structure.
• Gonioscopy (gonioscope): Confirm that the angle is open. Exclude other causes of elevated intraocular pressure such as angle recession, angle closure, peripheral anterior synechiae, and neovascularization. It is recommended to examine the entire circumference using a Goldmann-type gonioscope.
• Tonometry: Accurate measurement of intraocular pressure using a Goldmann applanation tonometer. This syndrome may show significant diurnal variation, so multiple measurements at different times of day are recommended.
• Slit-lamp examination: Evaluation of cell-like structures in the anterior chamber. Check for keratic precipitates (KP) and anterior synechiae to differentiate from uveitis. Also assess the degree of anterior chamber flare.
• Systemic examination: Check for physical findings of atopic dermatitis or Marfan syndrome. Marfan syndrome shows characteristic findings such as tall stature, arachnodactyly, and lens dislocation.

Differential Diagnosis

This syndrome presents with elevated intraocular pressure and anterior chamber cells, so differentiation from the following diseases is necessary.

Differential Disease	Key Points for Differentiation
Iritis (anterior uveitis)	KP and anterior synechiae present. Responds to steroids.
Posner-Schlossman syndrome	Fine KP, mild flare. Responds to steroids.
Traumatic glaucoma	Angle recession findings present. Intraocular pressure does not decrease even after retinal reattachment.
Primary open-angle glaucoma	No anterior chamber cells. Intraocular pressure does not decrease even after retinal reattachment.

Differentiation from traumatic glaucoma and primary open-angle glaucoma is often difficult, but a decisive distinguishing feature is that in these diseases, intraocular pressure does not decrease even after retinal reattachment.

Q How do you search for retinal tears when the pupil cannot be dilated?

A

When the fundus is difficult to visualize due to poor mydriasis or lens diseases (cataract, dislocation, etc.), B-mode ultrasonography is used to confirm the presence of retinal detachment. Furthermore, ultrasound biomicroscopy (UBM) can evaluate tears near the ciliary body and retinal detachment. OCT is also useful for detecting subretinal fluid. Scleral depression with an indentor may detect peripheral tears even when mydriasis is insufficient.

5. Standard Treatment

Treatment Principles

The fundamental treatment for this syndrome is retinal reattachment surgery. By repairing the rhegmatogenous retinal detachment, which is the source of photoreceptor outer segments, the cause of trabecular obstruction is removed, and intraocular pressure normalizes.

Surgical Therapy

• Scleral buckling surgery (scleral indentation): First choice. Since peripheral tears are common in young patients, scleral buckling is the most suitable procedure. Buckling materials such as silicone sponges or silicone bands are sutured onto the scleral surface to elevate the tear site externally and reattach the retinal pigment epithelium and neurosensory retina. Cryopexy is applied around the tear to promote adhesion. In young patients, the vitreous is clear and retinal flexibility is preserved, so good reattachment rates can be expected with scleral buckling.
• Vitrectomy (pars plana vitrectomy): Selected when proliferative vitreoretinopathy (PVR) is present, in cases of giant tears, or when reattachment is difficult with scleral buckling. After vitrectomy, laser photocoagulation is performed around the retinal tear, and tamponade is achieved with sulfur hexafluoride (SF6) gas or perfluoropropane (C3F8) gas. In severe cases, silicone oil tamponade may be chosen.
• Combined cataract surgery: When cataract or lens dislocation is present, lens reconstruction (intraocular lens implantation) may be performed simultaneously. Especially when fundus visualization is difficult due to lens opacity, simultaneous cataract surgery is considered to ensure visibility during surgical manipulation.

The European Glaucoma Society guidelines (5th edition) also state that surgery for retinal detachment is the mainstay of treatment, and glaucoma surgery should be considered when intraocular pressure control is poor⁴⁾.

Pharmacotherapy (Temporary Intraocular Pressure Reduction)

The following medications are used for intraocular pressure management while awaiting surgery.

• Carbonic anhydrase inhibitors: Acetazolamide (Diamox) 500 mg twice daily orally. Suppresses aqueous humor production and lowers intraocular pressure.
• Topical intraocular pressure-lowering agents: Beta-blockers (e.g., timolol 0.5%), prostaglandin analogs, etc., used as eye drops to lower intraocular pressure.
• Pilocarpine (off-label use): May widen the trabecular meshwork spaces through miosis and promote aqueous humor outflow.

Corticosteroids are ineffective. The “cells” in the anterior chamber are not inflammatory cells but photoreceptor outer segments; therefore, the anti-inflammatory effect of steroids does not reduce anterior chamber cells and does not improve intraocular pressure. This point is clinically extremely important: if steroid treatment is continued due to misdiagnosis as uveitis, no improvement is obtained, which may serve as a diagnostic clue.

Management of Treatment-Resistant Cases

If intraocular pressure remains poorly controlled after retinal reattachment, consider the following:

• Filtration surgery (e.g., trabeculectomy): Mitomycin C-augmented trabeculectomy surgically creates a new aqueous humor outflow pathway to lower intraocular pressure.
• Minimally invasive glaucoma surgery (MIGS): Microhook trabeculotomy or stent devices such as iStent reduce outflow resistance at the trabecular meshwork level. These have a lower risk of complications compared to conventional filtration surgery.
• Aqueous outflow pathway reconstruction: Trabeculotomy improves aqueous outflow into Schlemm’s canal.

However, persistent poor intraocular pressure control after successful retinal reattachment is uncommon. Even if intraocular pressure does not normalize early postoperatively, it may take several weeks for the photoreceptor outer segments to be cleared from the trabecular meshwork, and improvement may be observed during follow-up.

Treatment Considerations

Steroid eye drops do not improve anterior chamber cells or intraocular pressure. If steroid treatment is continued for a long period due to misdiagnosis as uveitis, there is an added risk of steroid-induced glaucoma and cataract progression. If anterior chamber cells do not respond to steroids, the presence of rhegmatogenous retinal detachment should be actively suspected.

Q Do steroid eye drops lower intraocular pressure?

A

No, they do not. The anterior chamber cells in this syndrome are not inflammatory cells but photoreceptor outer segments, so the anti-inflammatory effect of steroids is ineffective. On the contrary, long-term steroid use increases the risk of steroid-induced glaucoma and cataracts, so caution is needed. To lower intraocular pressure, oral carbonic anhydrase inhibitors (acetazolamide 500 mg twice daily) or beta-blocker eye drops should be used, and definitive treatment with retinal reattachment surgery is necessary.

6. Pathophysiology and Detailed Mechanism

Intraocular Pressure Changes in Typical Rhegmatogenous Retinal Detachment

Typically, when rhegmatogenous retinal detachment occurs, intraocular pressure tends to decrease ⁶⁾. This is because the exposed retinal pigment epithelium (RPE) actively absorbs fluid (pump action). Increased fluid absorption by the RPE promotes relative outflow compared to aqueous humor production, resulting in lower intraocular pressure.

Paradoxical Intraocular Pressure Elevation in This Syndrome

In this syndrome, intraocular pressure rises contrary to this normal rule. The mechanism is understood as follows.

1. Development of rhegmatogenous retinal detachment: Liquefied vitreous flows into the subretinal space through a retinal tear, causing retinal detachment.
2. Shedding of photoreceptor outer segments: Outer segments detach from photoreceptors in the detached retina and become free in the subretinal space.
3. Reaching the anterior chamber: The shed photoreceptor outer segments pass through the retinal tear along with viscous subretinal fluid, travel through the vitreous cavity, and reach the anterior chamber.
4. Blockage of the trabecular meshwork: The photoreceptor outer segments that reach the anterior chamber physically block the pores of the trabecular meshwork, the aqueous humor outflow pathway.
5. Aqueous outflow obstruction and intraocular pressure elevation: Blockage of the trabecular meshwork impairs aqueous outflow, leading to elevated intraocular pressure.

Role of the Vitreous Base

Shallow retinal detachments involving the vitreous base particularly increase the risk of developing this syndrome. Shallow detachment promotes continuous shedding of degenerated photoreceptor outer segments, and involvement of the vitreous base compromises the barrier function of the vitreous membrane, allowing photoreceptor outer segments to reach the anterior chamber unimpeded. In deep retinal detachments, photoreceptor outer segments are more likely to be trapped by the vitreous membrane, hindering their access to the anterior chamber.

Historical Hypotheses on the Etiology

Several hypotheses have been proposed regarding the etiology of this syndrome, as follows.

• Schwartz (1973): Hypothesized that iridocyclitis reduces the function of the aqueous outflow facility, contributing to intraocular pressure elevation under conditions of normal or decreased aqueous production²⁾.
• Davidorf (1978): Proposed that pigment granules released from the retinal pigment epithelium (RPE) migrate forward into the anterior chamber and block the trabecular meshwork⁵⁾.
• Matsuo et al. (1986, 1994): Isolated and identified photoreceptor outer segments and inflammatory cells from aspirated aqueous humor⁸⁾. They elucidated the pathogenic mechanism in which photoreceptor outer segments pass through a retinal tear, reach the aqueous outflow pathway, and cause outflow obstruction³⁾⁷⁾.

In case reports accumulated before the reports by Matsuo et al., the following three features were observed in the angle of this syndrome.

1. The degree of pigmentation is equal to that of the contralateral eye (no hyperpigmentation)
2. No pigmentation on the cornea
3. No floating pigment in the anterior chamber

These findings were inconsistent with Davidorf’s pigment granule theory and supported the notion that photoreceptor outer segments are the fundamental cause. This hypothesis was established by experimental evidence from Matsuo et al., and the term “Schwartz-Matsuo syndrome” has since become established ³⁾.

Normalization of intraocular pressure after retinal reattachment

When the retinal break is closed by retinal reattachment surgery, the supply of photoreceptor outer segments to the anterior chamber is blocked. Photoreceptor outer segments already deposited in the trabecular meshwork are gradually removed by phagocytosis of trabecular cells, and aqueous humor outflow is restored. As a result, intraocular pressure normalizes and anterior chamber cells disappear. This mechanism of intraocular pressure normalization progresses in stages as follows.

1. Closure of the retinal break stops the new supply of photoreceptor outer segments
2. Photoreceptor outer segments floating in the anterior chamber gradually decrease with aqueous humor turnover
3. Photoreceptor outer segments trapped in the trabecular meshwork are removed by phagocytosis of trabecular cells
4. Aqueous humor outflow resistance normalizes, and intraocular pressure returns to the physiological range

Intraocular pressure-lowering medications are rarely needed after surgery. This normalization of intraocular pressure is the most important clinical feature of this syndrome and provides a basis for differentiation from traumatic glaucoma and primary open-angle glaucoma. In traumatic glaucoma, structural damage to the trabecular meshwork due to angle recession is irreversible, and in primary open-angle glaucoma, age-related changes in the trabecular meshwork are the underlying cause, so intraocular pressure does not normalize after retinal reattachment in either condition.

Q Why does intraocular pressure decrease in ordinary retinal detachment but increase in this syndrome?

A

In ordinary rhegmatogenous retinal detachment, intraocular pressure decreases because the exposed retinal pigment epithelium (RPE) actively absorbs fluid ⁶⁾. However, in Schwartz syndrome, photoreceptor outer segments shed from the detached retina pass through the retinal break into the anterior chamber and physically obstruct the pores of the trabecular meshwork. This obstruction impairs aqueous humor outflow, resulting in an intraocular pressure increase that outweighs the pressure-lowering effect of RPE fluid absorption. Particularly in shallow detachments involving the vitreous base, photoreceptor outer segments easily reach the anterior chamber, increasing the risk of intraocular pressure elevation.

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