Glaucoma in uveitis: characteristics, diagnosis, and treatment

Uveitic glaucoma is a secondary glaucoma that occurs due to intraocular inflammation. Inflammatory mediators and structural changes in the trabecular meshwork increase resistance to aqueous humor outflow, leading to a persistent increase in intraocular pressure and damage to the optic nerve. Unlike primary glaucoma, the underlying cause is inflammation, and successful treatment directly depends on controlling uveitis activity. [1]

The disease syndrome is heterogeneous: pressure may increase paroxysmally or persist continuously, the anterior chamber angle may remain open or close due to posterior and anterior synechiae, and the contribution of drug-induced mechanisms depends on the anti-inflammatory agents used. This variability explains why these patients more often require surgical methods to reduce pressure and why standard treatments for primary open-angle glaucoma are less effective. [2]

A modern approach involves simultaneously suppressing inflammation and safely lowering intraocular pressure. In infectious causes, such as cytomegalovirus-induced anterior uveitic glaucoma, the key to success is timely antiviral therapy, which reduces the frequency of relapses and the risk of requiring glaucoma surgery. [3]

Clinical decisions should be aligned with current guidelines for the management of glaucoma and uveitis. The European Glaucoma Society's 2025 edition emphasizes the need for individualized care, while the American Academy of Ophthalmology describes quality standards for ophthalmic care and preferred clinical patterns that can be usefully adapted to uveitic glaucoma. [4]

Code according to ICD-10 and ICD-11

In the International Classification of Diseases, Tenth Revision, uveitic glaucoma is coded in block H40.4 "Glaucoma secondary to inflammation of the eye" with specification of the side and stage. Examples: H40.41X0 - "right, stage unspecified", H40.42X2 - "left, moderate stage", H40.43X3 - "bilateral, severe stage". The seventh position indicates the stage: 1 - mild, 2 - moderate, 3 - severe, 4 - stage unspecified. [5]

The International Classification of Diseases, Eleventh Revision, uses code 9C61.24, "Glaucoma due to ocular inflammation," which falls under the section "secondary open-angle glaucoma." "Glaucomatocyclic crisis" is separately identified as an independent nosological entity within this subsection. This level of detail helps standardize the diagnosis and statistical reporting of uveitic forms. [6]

Table 1. ICD-10 and ICD-11 codes for uveitic glaucoma

System	Chapter	Code	Description
ICD-10	Glaucoma	H40.4	Glaucoma secondary to inflammation of the eye
ICD-10	Clarification	H40.41X_	Right, with the stage indicated in the seventh position
ICD-10	Clarification	H40.42X_	Left, with the stage indicated in the seventh position
ICD-10	Clarification	H40.43X_	Double-sided, with indication of stage
ICD-11	Secondary open-angle	9C61.24	Glaucoma due to inflammation of the eye
ICD-11	Secondary open-angle	9C61.25	Glaucomatocyclic crisis
[7]

Epidemiology

According to large observational data from recent years, elevated intraocular pressure and glaucoma are common in patients with uveitis. In retrospective series and reviews, the proportion of uveitic glaucoma among chronic uveitis cases is approximately 15-20%, although results vary due to heterogeneity of definitions and populations. [8]

At the general population level, the estimated cumulative prevalence of uveitic glaucoma per decade was approximately 27 per 100,000, and the cumulative incidence was approximately 5 per 100,000, with approximately 15% of patients with established uveitis developing glaucoma within 10 years. These rates have shown a downward trend compared to early periods, likely due to better inflammatory control.[9]

According to a multicenter analysis, the annual incidence of elevated intraocular pressure in adults with non-infectious uveitis was approximately 14% per year, and the combined prevalence of uveitic elevated pressure and glaucoma was approximately 16%. Given the heterogeneity of etiologies and localizations, the risk varies between anterior, intermediate, and posterior uveitis. [10]

In children, the overall incidence of secondary glaucoma is comparable to that in adults, but the prognosis is worse due to the greater vulnerability of the optic nerve and a longer life expectancy. This requires lower target pressure levels and more frequent follow-up in pediatric patients. [11]

Table 2. Epidemiological landmarks

Indicator	Grade
The proportion of uveitic glaucoma among chronic uveitis	15-20%
Cumulative incidence in the population over 10 years	≈ 5 per 100,000
Cumulative prevalence in the population over 10 years	≈ 27 per 100,000
Annual incidence of high blood pressure in non-infectious diseases	≈ 14%
Risk in children compared to adults	Comparable in frequency, worse in prognosis
[12]

Reasons

The key cause is inflammatory damage to the trabecular meshwork and surrounding tissues, which increases outflow resistance and pressure. Cellular infiltrate, protein exudate, extracellular matrix deposition, trabecular remodeling, and adhesion formation contribute. With prolonged progression, scarring of the outflow tract develops. [13]

Steroid-induced hypertension is superimposed on the inflammatory mechanism. A glucocorticosteroid reaction is common, especially with the use of potent topical steroids and high cumulative doses, and can be a dominant factor in some patients. Discontinuation or de-escalation of steroids without adequate anti-inflammatory support carries the risk of uveitis recurrence, so switching to steroid-sparing immunosuppression is often necessary. [14]

Infectious forms of anterior uveitis, particularly cytomegalovirus, are associated with severe hypertension and the risk of uveitic glaucoma. A positive polymerase chain reaction for cytomegalovirus in the aqueous humor is often detected in clinical presentations resembling Posner-Schlossman crisis or Fuchs uveitis. In such situations, antiviral therapy significantly reduces the recurrence rate and the need for surgery. [15]

Additional causes include mechanical pupillary block due to angle-closure synechiae, postoperative conditions, uveitis-glaucoma-hyphema syndrome due to implant-iris interactions, and mediated systemic diseases such as sarcoidosis and seronegative spondyloarthritis. The multiplicity of causes dictates an individualized diagnostic approach and targeted causal therapy. [16]

Risk factors

The risk increases with chronic anterior uveitis, granulomatous inflammation, and severe adhesion formation. The more frequent and prolonged the active phase of inflammation, the higher the likelihood of persistent pressure increase and structural damage to the trabeculae. These observations are supported by both clinical series and general reviews. [17]

Steroid sensitivity is one of the most powerful modifiable risk factors. Adverse factors include the need for frequent strong steroid drops, multiple periocular injections, and long courses of systemic medications without switching to a steroid-sparing regimen. A family history of glaucoma and young age increase the likelihood of significant pressure increases with steroid use. [18]

Infectious anterior uveitis, particularly cytomegalovirus-associated uveitis, is associated with higher pressure peaks and frequent relapses. In regions with high cytomegalovirus seroprevalence, these forms are more common, which has implications for screening and the selection of etiotropic therapy. [19]

Concomitant macular pathology, including cystoid macular edema, and severe synechial angle organization are also factors associated with an unfavorable course. These conditions are associated with a higher risk of structural complications and decreased visual acuity, which worsens outcomes even with adequate pressure control. [20]

Table 3. Risk factors for uveitic glaucoma

Factor	Comment
Chronic and granulomatous anterior uveitis	High frequency of pressure rise
Steroid sensitivity and high cumulative dose of steroids	Modifiable factor
Cytomegalovirus anterior uveitis	Frequent relapses, high pressure peaks
Synechiae and angle closure	Mechanical pressure boosting component
Macular complications	Associated with worse functional outcome
[21]

Pathogenesis

Inflammatory activation leads to infiltration of the trabecular meshwork by immune cells, the release of interleukins and tumor necrosis factor, and disruption of trabecular cell metabolism. This increases extracellular matrix deposition, alters the cytoskeleton, increases trabecular rigidity, and, consequently, outflow resistance. Simultaneously, inflammation damages retinal ganglion cell axons. [22]

With prolonged progression, posterior synechiae and pupillary block develop, leading to relative or absolute closure of the angle and "trapping" the high pressure. In some cases, a steroid-induced component is added to the inflammatory component due to altered expression of outflow proteins, which exacerbates the increased pressure even in a "quiet" eye. [23]

Certain viruses, particularly cytomegalovirus, can infect structures of the anterior segment, damage the corneal endothelium and trabecular meshwork, and trigger attacks of sharply elevated pressure. This explains the recurrent course with prolonged lucid intervals and the need for etiotropic antiviral therapy in confirmed infections. [24]

The result is a multifactorial "inflammatory trabeculopathy," which combines immune, mechanical, and drug-induced mechanisms. This understanding underlies a strategy of simultaneously suppressing inflammation and reducing pressure, as well as early surgical planning when signs of scarring and inadequate response to drops are present. [25]

Symptoms

Classic symptoms of uveitis include redness, photophobia, lacrimation, and pain of varying intensity, sometimes accompanied by blurred vision. With persistent increased pressure, rainbow-like halos appear around light sources and a feeling of fullness in the eye. In some patients, increased pressure is asymptomatic and is only detected upon examination. [26]

Cytomegalovirus-positive forms and so-called glaucomatocyclic crises are characterized by repeated attacks of sharply elevated pressure with relatively moderate inflammation. Attacks may resolve spontaneously, but they recur and, without preventive therapy, lead to cumulative damage to the optic nerve. [27]

If posterior synechiae and pupillary block develop, pain, nausea, and a sharp decrease in vision develop, requiring emergency care. Chronic open-angle uveitic glaucoma often results in a gradual narrowing of the visual field and decreased contrast sensitivity without severe acute pain. [28]

Complications of uveitis itself are also common, including cystoid macular edema, cataracts, and epiretinal membranes, which impair vision and affect the effectiveness of antiglaucoma therapy. Glaucoma progression itself should be distinguished from inflammatory and macular causes of visual acuity loss. [29]

Classification, forms and stages

Based on the mechanism, open-angle uveitic glaucoma is classified as trabecular inflammatory inflammatory glaucoma, steroid-induced open-angle glaucoma, and synechial-blockade glaucoma with angle closure. A separate clinical group includes recurrent "glaucomatocyclic crisis," in which acute pressure surges are combined with mild anterior uveitis. [30]

Based on etiology, a distinction is made between non-infectious autoimmune forms, infectious forms confirmed by polymerase chain reaction, postoperative, and rare mechanical forms, such as uveitis-glaucoma-hyphema syndrome due to lens or drainage interaction with the iris. This distinction helps select causal therapy and predict the risk of recurrence. [31]

Glaucoma staging is based on optic nerve head status, optical coherence tomography (OCT) thickness, and visual field stability. In ICD-10, the stage is coded in the seventh position, which is important for reporting and patient routing. [32]

Table 4. Clinical classification of uveitic glaucoma

Base	Option	Key mechanism
Mechanism	Open-angle inflammatory	Inflammatory trabeculopathy
Mechanism	Steroid-induced	Drug-induced changes in outflow
Mechanism	Synechial block	Pupil block, angle closure
Etiology	Non-infectious	Autoimmune diseases
Etiology	Infectious	Cytomegalovirus, herpes viruses
Special form	Glaucomatocyclic crisis	Attacks of increased pressure in mild uveitis
[33]

Complications and consequences

Without adequate control of inflammation and pressure, progressive glaucomatous optic neuropathy develops with irreversible visual field loss. The risk of accelerated deterioration is higher than with primary glaucoma due to repeated pressure peaks and fibrotic changes in the outflow tract. Therefore, target pressure levels are often set 2-4 mmHg lower than the standard for a comparable stage. [34]

Frequent complications of uveitis include cystoid macular edema, cataracts, and epiretinal membranes, which impair visual acuity regardless of pressure. These factors should guide treatment strategies, such as the choice of steroid-sparing therapy, to minimize the risk of biased outcome assessment. [35]

Surgical treatment in patients with active or recent uveitis is associated with higher risks of filter bleb fibrosis and shunt failure. To reduce this risk, it is essential to achieve a "quiet" eye prior to surgery and carefully monitor inflammation postoperatively. [36]

In cytomegalovirus-associated forms, without etiotropic therapy, relapses lead to corneal decompensation and a high probability of surgery. Antiviral regimens reduce the frequency of relapses and delay the need for drainage device implantation. [37]

When to see a doctor

Immediate treatment is necessary if you experience severe eye pain, sudden loss of vision, nausea, or the appearance of rainbow-colored rings around lights—these are signs of a sudden increase in pressure or pupillary block. Delay can lead to irreversible vision loss. [38]

Patients with established uveitis should undergo an unscheduled examination whenever redness, photophobia, and blurred vision recur, as active inflammation is often accompanied by pressure surges. An early visit allows for timely adjustments to therapy. [39]

Any increase in topical steroids requires more frequent pressure monitoring, especially in individuals with a prior steroid reaction or a family history of glaucoma. Monitoring is also necessary after steroid discontinuation, as elevated pressure may persist for weeks. [40]

If you experience recurrent episodes of high blood pressure associated with mild anterior uveitis, discuss with your doctor testing your aqueous humor for cytomegalovirus using polymerase chain reaction. Confirmation of infection changes the treatment plan and adds antiviral therapy. [41]

Diagnostics

The first step is to confirm glaucomatous damage and assess the activity of uveitis. Tonometry, biomicroscopy to assess cells and protein in the anterior chamber, gonioscopy to detect adhesions and angle status, examination of the optic disc, perimetry, and optical coherence tomography of the nerve fiber layer are performed. These methods allow for simultaneous staging of glaucoma and assessment of inflammatory activity. [42]

The second step is to identify the cause and phenotype. If an infectious cause is suspected, a diagnostic anterior chamber puncture with polymerase chain reaction testing for cytomegalovirus, herpes simplex virus, and varicella-zoster virus is considered. For non-infectious forms, systemic markers and imaging are used as indicated. [43]

The third step is an assessment of mechanical and drug factors. The degree of adhesions, the presence of pupillary block, the angle width, and current and past glucocorticosteroid exposure are documented, along with an assessment of the likelihood of a steroid reaction. This analysis helps determine the sequence of interventions, from iridotomy to early surgical planning. [44]

The fourth step is basic laboratory and instrumental stratification based on concomitant macular pathology and inflammatory complications. Optical coherence tomography of the macula, disc imaging, central corneal thickness measurement, and dynamic visual field testing are performed as indicated. This is important for target pressure selection and progression monitoring. [45]

Table 5. Step-by-step diagnostic algorithm

Step	Target	Tools
1. Confirm glaucoma and assess uveitis activity	Staging, inflammation activity	Tonometry, slit lamp, gonioscopy, perimetry, optical coherence tomography
2. Clarify the etiology	Infectious or non-infectious nature	Polymerase chain reaction of aqueous humor, systemic tests as indicated
3. Disassemble the mechanical and medicinal contribution	Intervention plan	Gonioscopy for synechiae and angle, drug history of steroids
4. Record any associated complications	Correction of the treatment goal	Optical coherence tomography of the macula, disc photography, field tests
[46]

Differential diagnosis

True uveitic glaucoma should be distinguished from transient uveitic ocular hypertension without signs of glaucomatous neuropathy. In the latter case, with complete control of inflammation and a reduction in pressure, structural and functional changes do not progress, which influences the choice of duration and intensity of therapy. [47]

It is necessary to distinguish between drug-induced steroid-induced glaucoma without active uveitis and the inflammatory open-angle form. A detailed medication history, a trial of steroid de-escalation against the background of immunosuppression, and pressure dynamics provide the key to the correct classification. [48]

A separate challenge is distinguishing between glaucomatocyclic crisis and herpesvirus-induced anterior uveitis. Clinical signs and polymerase chain reaction are helpful here; if cytomegalovirus is confirmed, etiotropic drugs are added, which reduces relapses and lowers the cumulative risk of nerve damage. [49]

Rare mechanical causes are also considered, including uveitis-glaucoma-hyphema syndrome after implant surgery. Correct identification of the mechanical factor may lead to implant revision or repositioning rather than escalation of antiglaucoma therapy. [50]

Table 6. Differential features

State	Inflammatory activity	Pressure peaks	Etiotropic therapy
Uveitic glaucoma	Is there or was there recently?	Often resistant	Anti-inflammatory plus anti-glaucoma
Transient ocular hypertension in uveitis	Eat	Temporary	Control of uveitis, sometimes without long-term drops
Steroid-induced glaucoma	No	Resistant to steroid exposure	Steroid-sparing regimens
Glaucomatocyclic crisis	Light	Attacks	Consider antiherpes or anticytomegalovirus therapy
Uveitis-glaucoma-hyphema syndrome	Variable	Variable	Surgical tactics according to indications
[51]

Treatment

The first principle is active inflammation suppression, otherwise any reduction in pressure will be unstable. For anterior forms, treatment begins with topical steroids of sufficient potency, followed by a gradual reduction in the frequency of instillations under slit lamp and pressure monitoring. When the posterior segment is involved, short-term systemic steroids are added, with an early transition to a steroid-sparing regimen. [52]

The choice of topical steroid is important: difluprednate is more potent, penetrates better, and relieves inflammation more quickly, but it more often increases blood pressure and requires caution in individuals at risk for a steroid reaction. Prednisolone acetate remains the first-line standard, while difluprednate is used in severe cases and under closer blood pressure monitoring. [53]

In non-infectious uveitis, immunosuppressants are used to reduce the steroid load. Methotrexate and mycophenolate mofetil have proven efficacy as steroid-sparing agents, with methotrexate demonstrating a higher rate of inflammation control at 6 months in several studies. The choice of drug depends on the safety profile, comorbidities, and fertility plans. [54]

Adalimumab, a targeted tumor necrosis factor inhibitor, is increasingly being used in refractory disease and pediatrics. It is indicated for intermediate, posterior, and panuveitis in adults and children aged 2 years and older. In cases of insufficient response, dose escalation or switching to other biologic agents, such as infliximab or tocilizumab, is discussed. The decision to escalate is made by a multidisciplinary team. [55]

For cytomegalovirus-positive anterior uveitis, antiviral therapy with ganciclovir or valganciclovir, administered topically or systemically, is recommended. Studies show reduced recurrence rates, better pressure stabilization, and a reduced risk of ocular surgery, especially with early treatment initiation. The choice of administration method and course duration is individualized. [56]

Antiglaucoma drops are selected in parallel with anti-inflammatory treatment. Beta-blockers, carbonic anhydrase inhibitors, and alpha-agonists are most commonly used. Prostaglandin analogs have traditionally been prescribed with caution due to concerns about increased inflammation, but a large analysis has shown a low incidence of induced uveitis and comparable safety with stable inflammation control; the decision is made on an individual basis. Miotics are generally avoided due to the risk of increased inflammation and stimulation of adhesions. [57]

In cases of pupillary block due to posterior synechiae, peripheral laser iridotomy is performed after preliminary lubrication and relief of active inflammation. In patients with an open angle and a poor response to drops, when the eye is "quiet," selective laser trabeculoplasty is considered as an adjunctive option, supported by new safety data in patients with uveitic glaucoma. [58]

Minimally invasive outflow tract interventions have become widespread as conjunctiva-preserving methods, particularly in young patients and those previously untreated. Double-blade excisional goniotomy and combined phacotherapy can reduce pressure and drug load in some patients with open angles, although efficacy is limited in certain conditions, such as Fuchs uveitis. The choice of method depends on the uveitis phenotype and angle status. [59]

If drops and laser treatments are unsuccessful, filtration surgery is considered. Trabeculectomy with mitomycin C is effective provided the eye is "quiet" before and after surgery with active anti-inflammatory therapy; however, the risk of scarring and failure is higher than with primary glaucoma. The decision to choose filtration surgery is made taking into account plans for future interventions and the condition of the conjunctiva. [60]

Glaucoma drainage devices remain a mainstay strategy in refractory patients. Comparative studies show that the Baerveldt implant can provide lower pressures than the Ahmed valve, at the cost of a higher incidence of hypotension and other complications; the choice of device depends on the pressure goal and risk profile. Anecdotal studies demonstrate similar results between modern drainage models, and management of the "hypertensive phase" after implantation improves long-term success. Cyclophotocoagulation is considered an option in cases of failure and in patients with a high surgical burden. [61]

Prevention

The best prevention is stable uveitis control with early transition to steroid-sparing regimens if long-term treatment is necessary. This reduces cumulative steroid exposure and decreases the risk of persistent hypertension. Collaboration between an ophthalmologist and rheumatologist increases the likelihood of remission without high-dose steroids. [62]

Patients receiving topical or systemic steroids require regular blood pressure monitoring: at the start of therapy, then after 2-4 weeks, and then as clinically indicated. If a steroid reaction is detected, the regimen is adjusted, an immunosuppressant is added, and topical medications with a lower risk of affecting blood pressure are reviewed. [63]

In confirmed cytomegalovirus-induced anterior uveitis, etiotropic antiviral therapy reduces the incidence of relapses and decreases the likelihood of surgery. The choice between local and systemic regimens, as well as the duration of maintenance treatment, is determined by the risk of relapse and tolerability. [64]

Patient education is an integral part of prevention: recognizing early symptoms of exacerbation, adhering to the instillation regimen, and attending an unscheduled examination if any worsening occurs. This is especially important for individuals with recurrent episodes of high blood pressure. [65]

Forecast

The prognosis is determined by the speed and completeness of inflammation control, achieving target pressure, and the timely use of surgery if eye drops fail. On average, uveitic glaucoma is more aggressive than primary forms, but with modern tactics, including steroid-sparing methods and advanced surgical technologies, it is possible to stabilize the process in most patients. [66]

The presence of an infectious factor worsens the prognosis without causal therapy; however, with early administration of antiviral drugs, outcomes improve significantly. This further underscores the value of molecular diagnostics in ambiguous clinical situations. [67]

The high risk of fibrosis after filtration surgeries requires long-term observation and readiness for additional interventions. Proper surgical planning in a "quiet" eye with aggressive inflammation control increases the chances of long-term success. [68]

Functional outcomes depend not only on pressure but also on concomitant complications of uveitis, so an integrated strategy that takes into account macular status and optical media transparency most fully reflects the real clinical picture. [69]

FAQ

Can prostaglandin analogues be used in uveitic glaucoma? Historically, they have been avoided due to concerns about increasing inflammation, but large data show a low incidence of drug-induced uveitis; with stable inflammation control and an individual risk assessment, these drugs can be considered. The decision is made on a personalized basis, with early assessment of response and tolerability. [70]

What's more important: first suppressing inflammation or immediately reducing pressure? Both approaches are critical, but suppressing active uveitis is paramount, otherwise any antiglaucoma measures will be unstable. In practice, anti-inflammatory treatment is initiated immediately, while pressure-reducing drops are simultaneously selected. [71]

When to consider surgery? If, in a "quiet" eye, the pressure remains above the target despite optimal drops and laser, if synechiae form with the risk of angle closure, or if repeated pressure peaks occur due to relapses, filtration surgery or drainage implantation should be considered. It is important to ensure minimal uveitis activity before and after surgery. [72]

Does selective laser trabeculoplasty help? In carefully selected patients with an open angle and stable inflammation, selective laser trabeculoplasty can reduce pressure and the need for eye drops. This method is considered adjunctive and does not replace anti-inflammatory treatment. [73]

Is there a role for minimally invasive surgery? In patients with open angles and remitted inflammation, minimally invasive procedures are used as conjunctiva-sparing options, although the data are mixed and depend on the diagnosis. In Fuchs uveitis, the effectiveness of individual techniques is lower, which is taken into account when choosing a method. [74]

How does antiviral therapy affect outcomes in cytomegalovirus uveitis? Antiviral drugs reduce the frequency of relapses, more quickly control inflammation, and decrease the need for surgery. The choice between topical and systemic regimens is determined by clinical presentation and tolerability. [75]