Hemodialysis (HD) is a major renal replacement therapy for patients with end-stage renal disease (ESRD), typically performed for about 12 hours per week. It has long been reported that transient intraocular pressure (IOP) elevation can occur during HD, a phenomenon named “ocular dialysis disequilibrium (ODD)” by Lippold et al. 1).
The mechanism lies in the rapid removal of osmotically active substances such as urea from the plasma during dialysis. While plasma osmolality decreases, the decrease in aqueous humor osmolality lags behind, making the aqueous humor relatively hyperosmotic compared to plasma. This osmotic gradient causes water to move from the vascular space into the aqueous humor, increasing IOP1).
In individuals with normally functioning aqueous outflow pathways, increased drainage through Schlemm’s canal compensates and IOP remains stable. However, in patients with impaired outflow, such as those with narrow-angle glaucoma or neovascular glaucoma, the increased aqueous volume cannot be adequately drained, potentially leading to pathological IOP elevation 1).
QAre all patients undergoing hemodialysis at risk for IOP elevation?
A
Not all patients experience clinically significant IOP elevation. If the aqueous outflow pathways function normally, compensatory mechanisms stabilize IOP. High-risk patients include those with narrow angles, neovascular glaucoma, pre-existing glaucoma, or iris-corneal angle damage due to diabetic proliferative retinopathy. Advances in dialysis technology (e.g., change from acetate to bicarbonate) may have reduced the impact on IOP in recent years.
In a case report, the left eye with neovascular glaucoma showed an intraocular pressure elevation of 36–43 mmHg during dialysis, while the right eye with a normal angle did not show a significant increase 1). This difference reflects the difference in functional reserve of the aqueous humor outflow pathway.
Narrow angle/angle closure: Baseline angle narrowing increases the risk of intraocular pressure elevation during dialysis. The angle opening distance and trabecular-iris angle are associated with intraocular pressure changes.
Neovascular glaucoma: Neovascularization of the iris and angle due to diabetic proliferative retinopathy impairs the aqueous humor outflow pathway and significantly increases the risk of ODD 1).
Pre-existing glaucoma: A 2021 meta-analysis showed that despite improvements in dialysis technology, a history of glaucoma is an independent factor for intraocular pressure elevation.
Dialysis-Related Risk Factors
Rapid decrease in plasma osmolality: Rapid removal of small molecular solutes such as urea at the start of dialysis creates an osmotic gradient 1).
Dialysate composition: Acetate dialysate may have a higher risk of intraocular pressure elevation compared to bicarbonate dialysate.
High urea removal rate: The risk increases when the initial plasma urea concentration is high and the urea removal rate is high 1).
Dialysis flow rate: When blood flow rate and dialysate flow rate are high, osmotic changes become rapid and the risk increases 1).
A large-scale case-control study in Taiwan showed that ESRD patients have a significantly higher risk of developing glaucoma (adjusted hazard ratio 1.270), especially angle-closure glaucoma (adjusted hazard ratio 1.550).
The diagnosis of ODD is made clinically and is a diagnosis of exclusion. The pattern is established when repeated intraocular pressure elevations during dialysis are confirmed and other neurological and ophthalmic diseases are excluded.
Intraocular pressure measurement during dialysis: IOP is measured before, during, and after dialysis using a portable tonometer (e.g., TonopenXL) 1). Routine outpatient intraocular pressure measurements may not capture the elevation during dialysis.
Gonioscopy: Evaluate the presence of neovascularization in the iris and angle, and assess angle closure1).
Anterior segment OCT: Useful for quantitative evaluation of angle structures (lens thickness, angle opening distance, trabecular-iris angle)1).
Topical intraocular pressure-lowering medications: Combinations of brimonidine, dorzolamide, timolol, etc.1). In ESRD patients, systemic administration of acetazolamide or mannitol is relatively contraindicated.
Anti-VEGF therapy: Intravitreal anti-VEGF injection promotes regression of neovascularization in neovascular glaucoma1).
Modification of dialysis prescription: Increase dialysate sodium concentration (145 mEq/L), decrease blood flow and dialysate flow to slow osmotic changes1). Multidisciplinary collaboration with nephrology is important.
Surgical Treatment
Glaucoma drainage device: Ahmed glaucoma drainage valve implantation is performed when medical treatment is insufficient1). Case reports describe Ahmed valve placement along with cataract surgery, vitrectomy, and retinal photocoagulation, resulting in resolution of symptoms during dialysis1).
Other considerations: Switching to high-flux HD or hemofiltration, administration of hyperosmolar glucose during dialysis, and switching to peritoneal dialysis have also been reported1).
QCan changes in dialysis prescription prevent intraocular pressure elevation?
A
Increasing dialysate sodium concentration or decreasing blood flow rate and dialysate flow rate may slow the rate of osmotic change, potentially reducing intraocular pressure elevation. However, case reports describe patients whose intraocular pressure remained unstable despite changes in dialysis prescription and maximal medical therapy, ultimately requiring surgery (Ahmed valve implantation). Modifying dialysis prescription is part of the treatment strategy but may be insufficient alone.
The pathophysiology of intraocular pressure changes during hemodialysis is explained as follows1).
Osmotically active substances such as urea have a large volume of distribution and are rapidly removed from plasma during dialysis. Sitprija et al. showed that intraocular pressure elevation during dialysis correlates with a decrease in plasma osmolality1). Because the decrease in aqueous humor osmolality lags behind that of plasma, the aqueous humor becomes relatively hyperosmotic compared to plasma, causing water to move from the vascular space into the aqueous humor.
In individuals with normal aqueous outflow pathways, aqueous drainage from Schlemm’s canal to the periorbital lymphatic vessels increases, compensating and stabilizing intraocular pressure1). In contrast, in patients with impaired angle, the drainage rate is insufficient, leading to intraocular pressure elevation.
On the other hand, some reports indicate that intraocular pressure decreases during dialysis. The proposed mechanism is that fluid removal increases plasma colloid osmotic pressure, enhancing the gradient via the uveoscleral outflow pathway and promoting aqueous outflow.
A 2021 meta-analysis found no significant overall association between intraocular pressure and hemodialysis, but subgroup analysis revealed an interesting temporal trend: studies before 1986 showed significant intraocular pressure elevation, those from 1986 to 2005 showed no change, and those after 2005 showed a decreasing trend. The shift from acetate to bicarbonate dialysate was identified as a moderating factor.
QCan intraocular pressure decrease after hemodialysis?
A
Yes, it has been reported. Fluid removal during dialysis increases plasma colloid osmotic pressure, which may enhance the osmotic gradient via the uveoscleral outflow pathway, promoting aqueous outflow and decreasing intraocular pressure. The 2021 meta-analysis also showed an overall decreasing trend in intraocular pressure in studies after 2005. Advances in dialysis technology and dialysate composition are thought to contribute to this change.
