The Effect of Dorzolamide-timolol Eye drop on Intraocular Pressure Change in Intravitreal Ranibizumab Injected Patients

Abstract:

PURPOSE:

The objective of the study was to examine the effect of dorzolamide–timolol (DT) eye drop used before intravitreal ranibizumab (IVR) injection on intraocular pressure (IOP) change.

METHODS:

50 eyes of 50 patients who received DT eye drops 1 h before IVR injection due to diabetic retinopathy and macular edema were considered Group 1, and 50 eyes of 50 patients who did not receive DT eye drops were considered Group 2. Those patients who had previously undergone intravitreal injection had intraocular surgery, and used any eye drops were not included in the study. Before the injection, IOP values were measured with a Tonopen contact handheld tonometer before the blepharostat was placed (BIOP), after the blepharostat was placed (AIOP), and at the 1^st min after the injection (IIOP).

RESULTS:

There were 25 males and 25 females in Group 1 and 25 males and 25 females in Group 2; the mean age was 65.66 ± 9.94 years in Group 1 and 65.54 ± 7.43 years in Group 2 (P = 0.98). In Group 1, BIOP was 18.91 ± 18.91, AIOP was 21.62 ± 6.16 mmHg, and IIOP was 49.21 ± 10.95 mmHg. In Group 2, BIOP was 20.18 ± 4.19 mmHg, AIOP was 24.60 ± 4.90 mmHg, and IIOP was 49.96 ± 9.72 mmHg. IIOP-BIOP difference was 30.30 ± 9.85 mmHg in Group 1 and 29.78 ± 9.33 mmHg in Group 2 and the difference was not statistically significant (P = 0.78). In Group 1, the IIOP-AIOP difference was 27.58 ± 10.60 mmHg and in Group 2, 25.36 ± 10.46 mmHg. The difference between IIOP and AIOP was not statistically significant (P = 0.27).

CONCLUSION:

The use of topical DT eye drops before IVR injection does not affect the intraocular pressure change.

Introduction

Intravitreal injection of antivascular endothelial growth factor (VEGF) is used in a wide spectrum of vitreoretinal diseases. Globally, the most used procedure for ophthalmological disorders is intravitreal injection. Although its safety has been demonstrated in many studies, it may cause various ocular adverse effects. One of these adverse effects is a sudden increase in intraocular pressure (IOP).[1,2] Recurrence of IOP elevations that may occur during injections may have important clinical consequences, particularly in patients having glaucoma and some retinal diseases where optic nerve reserve is weakened.[3]

Methods

In Karabük University Faculty of Medicine Training and Research Hospital Department of Ophthalmology, 100 eyes of 100 patients who received intravitreal ranibizumab (IVR) due to diabetic retinopathy and macular edema were evaluated after ethics committee approval. Fifty eyes of 50 patients who used topical dorzolamide–timolol (DT) eye drops 1 h before the intravitreal injection were considered Group 1, and 50 eyes of 50 patients who did not use topical DT were considered Group 2. Patients using ocular medications or with a history of previous surgery were not included in the study.

All injections were administered under operating room conditions following the same protocol. All injections were performed by the same surgeon and the same type of blepharostat was used in the patients. IOPs were measured with a Tonopen (Tono-pen XL tonometer, Mentor O and O Inc., Norwell, MA, USA) contact handheld tonometer. Following topical anesthesia, all patients underwent ocular surface cleaning with 10% povidone-iodine. After sterile drape and blepharostat placement, 3.5 mm from the limbus was marked and an IVR 0.05 mg/0.05 ml was injected by using a 30 G syringe tip. Following the injection, the entrance site was massaged with a cotton swab. Before blepharostat IOP (BIOP), after blepharostat IOP (AIOP), injection IOP (IIOP) values and both BIOP-IIOP differences and AIOP-IIOP differences were compared between the two groups.

Statistical analyses were performed using SPSS version 16.0 (SPSS Inc., Chicago, Illinois, USA), and a P < 0.05 was considered statistically significant. In the normal distribution test performed before the analysis, it was observed that the variables fit the normal distribution. The mean and standard deviation values of the groups were calculated. An independent t-test was used to compare the numerical variables of the two groups. Whether there was a difference between groups in terms of gender was evaluated with the Chi-square test.

Results

There were 25 male patients and 25 female patients in Group 1 and 25 male patients and 25 female patients in Group 2. The mean age was 65.66 ± 9.94 years in Group 1 and 65.54 ± 7.43 years in Group 2 (P = 0.98). In Group 1, IIOP was found to be 18.91 ± 4.97 mmHg, AIOP was 21.62 ± 6.16 mmHg, and IIOP was 49.21 ± 10.95 mmHg. In Group 2, IIOP was found to be 20.18 ± 4.19 mmHg, AIOP was 24.60 ± 4.90 mmHg, and IIOP was 49.96 ± 9.72 mmHg. While the IIOP-BIOP difference was found to be 30.30 ± 9.85 mmHg in Group 1, and 29.78 ± 9.33 mmHg in Group 2, and the difference was not statistically significant between the groups (P = 0.78). In Group 1, the IIOP-AIOP difference was 27.58 ± 10.60 mmHg, and in Group 2, 25.36 ± 10.46 mmHg; the difference was not statistically significant between the groups (P = 0.27) [Table 1]. IOP returned to normal values in all patients on the 1^st day after the injection.

Table 1.

The between-group comparisons of age, gender, and intraocular pressure values

	Group 1	Group 2	P
Age (years)	65.66±9.94	65.54±7.43	0.98
Sex (male, female)	25, 25	25, 25	1
BIOP (mmHg)	18.91±4.97	20.18±4.19	>0.05
AIOP (mmHg)	21.62±6.16	24.60±4.90	>0.05
IIOP (mmHg)	49.21±10.95	49.96±9.72	>0.05
IIOP-BIOP difference (mmHg)	30.30±9.85	29.78±9.33	0.78
IIOP-AIOP difference (mmHg)	27.58±10.60	25.36±10.46	0.27

BIOP: Before the blepharostat is placed, AIOP: After the blepharostat placed, IIOP: Injection on intraocular pressure

Discussion

During intravitreal injection, a sudden increase in IOP immediately after the injection is an expected event due to the increase in vitreous volume, and studies have reported that it may be temporary or permanent.[3,4,5,6] Intravitreal anti-VEGFs are thought to exit the vitreous cavity either through choroidal circulation or aqueous drainage.[7] These pathways ensure the normalization of increased IOP.

The only treatable risk factor in glaucoma is IOP, and in its measurement, Goldmann applanation tonometry is accepted as the gold standard. Tonopen electronic tonometer, which has become widely used in ophthalmology practice, is recommended as an alternative device to the Goldmann applanation tonometer.[8] It is a handheld applanation tonometer that is easy to calibrate and use and also allows IOP measurement in patients with corneal pathology. In comparative studies of Tonopen and Goldmann applanation tonometer, it was reported that Tonopen gave accurate results both in the normal population and in eyes with glaucoma.[9,10] We also used Tonopen in our study.

In a group of 70 patients who had never had an intravitreal injection before, intravitreal bevacizumab was administered with a 27 G needle and IVR was administered with a 30 G needle. Researchers have suggested that using a 30 G needle was more comfortable and that intravitreal bevacizumab should also be administered with a 30 G needle.[11] In 65 eyes, where postinjection vitreous reflux and IOP spike were evaluated using 30 G and 32 G needles in intravitreal anti-VEGF injection, in the 32 G needle group, higher IOP and less vitreous reflux were observed after injection.[12]

In a study performed by the participation of 530 retina specialists queried about the intravitreal anti-VEGF injection protocol, drug preference, injection technique, and long-term IOP elevation observations; 292 retina specialists responded that they believed that intravitreal anti-VEGF injection caused long-term IOP elevation, but their drug preference was not related to IOP elevation. It has been asserted that the sustained elevation of IOP in anti-VEGF injection may be caused by the use of rapid injection technique and high volume. Rapid IOP elevation may lead to this complication by causing trabeculum damage.[13]

In our study, we evaluated the effect of using topical DT drops 1 h before the procedure on the IOP change before and after injection in patients receiving IVR. No difference was observed between IOP values and IOP change in the groups with and without topical DT eye drop administration.

According to Kim et al.; in the short term after the injection, the intravitreal injection was well tolerated by the patients and it was observed that the IOP value in all patients decreased to normal values within 30 min without the need for any intervention. Recurrent or prolonged IOP monitoring after intravitreal injection was not considered necessary. However, it has been stated that injections of more than 0.05 ml with a thin needle, such as a 27 G that does not allow much vitreous reflux, or patients who do not experience postinjection vitreous reflux despite using a wider needle and those with a history of glaucoma may require postinjection IOP monitoring.[14] In our study, the tolerance of the patients was also good, and patients with a previous diagnosis of glaucoma were not included in our study. 0.05 mg/0.05 ml ranibizumab was administered using a 30 G syringe tip and 1 day later, IOP values were normal in all patients, but we think that careful monitorization of IOP is required in individuals with low optic nerve reserve, such as glaucoma patients.

Frenkel et al., on the other hand, recommended discontinuing the use of topical drops or systemic medication before intravitreal injections and applying paracentesis only to patients with previous sudden IOP elevation attacks, known optic nerve damage, and loss of light sensation within minutes after the injection.[15] In our study, there was no loss of light sensation and no anterior chamber paracentesis was required. In a double-blind placebo-controlled study by Theoulakis et al., placebo (artificial tear drops) or combigan (brimonidine–timolol) twice daily 1 day before the injection and on the day of the injection were administered into one eye of 88 patients with normotensive age-related macular degeneration in whom IVR injection is planned. IOP measurements were made before the procedure and 5, 10, 15 min, and 1 h after the procedure. As a result, IOP was found to be at normal values at the 1^st h after injection in all patients.[16]

Lee et al. have stated that they have encountered IOP above 30 mmHg in only two patients in the short term after intravitreal injection and that IOP decreased to normal levels within an hour without any pharmacological or surgical intervention.[17] Mojica et al. have found that none of the 50 eyes receiving IVR injection had IOP above 31 mmHg 30 min after the injection. The use of eye drops or anterior chamber paracentesis was not required in any eye after the injection to reduce IOP.[18] According to the study of Erol et al., no significant increases in IOP occurred in the early period after intravitreal injection of 4 mg/0.1 ml triamcinolone acetonide, and anterior chamber paracentesis was not required after the injections.[19]

IOP elevation is frequently observed after intravitreal injection, IOP can reach very high values and this elevation can be seen after all intravitreal injections. However, these IOP elevations are transient, and anterior chamber paracentesis is not required.

Conclusion

In our study, we aimed to evaluate the effect of topical DT eye drop use on the IOP change caused by the injection process in patients receiving IVR and found that antiglaucomatous eye drops did not affect the IOP change. Although IOP returned to normal in all patients on the 1^st day after the procedure, the limitation of our study is that we did not observe IOP values during the 1^st day after the procedure.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.