The Application Research on Iris-clip intraocular lens implantation for Aphakia in Canine

doi:10.21203/rs.3.rs-4664999/v1

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The Application Research on Iris-clip intraocular lens implantation for Aphakia in Canine

https://doi.org/10.21203/rs.3.rs-4664999/v1

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Objective

This study aimed to assess the clinical efficacy of Iris-clip intraocular lens (IOL) implantation for treating Aphakia in canines.

Method

Twelve dogs diagnosed with hereditary cataracts in both eyes were enrolled. Each dog's eyes were randomly assigned to either the control group or the operative group. Phacoemulsification was performed on both groups, with the operative group additionally receiving Iris-clip IOL implantation. Routine ophthalmic examinationst were conducted and compared between the two groups.

Results

In both groups, IOP gradually decreased post-surgery, with levels on the 3rd day being significantly lower than pre-surgery levels (P < 0.05). STT values initially decreased, then increased, with the operative group exhibiting lower values than normal between the 4th and 21st days post-surgery. Corneal edema and aqueous humor flare were higher in the operative group, requiring a longer recovery period. Visual acuity improved significantly in both groups, with the operative group showing superior results.

Conclusion

Iris-clip anterior chamber intraocular lens implantation may lead to early postoperative complications. However, with appropriate local drug treatment, these complications can be resolved, resulting in significant improvement in visual acuity in dogs with aphakic eyes. This study confirms the feasibility of this surgical approach for treating aphakia in dogs.

Biological sciences/Zoology/Animal physiology

Biological sciences/Biotechnology/Animal biotechnology

Health sciences/Diseases/Eye diseases/Lens diseases

Aphakia

Iris-clip intraocular lens

feasibility

Canine

The lens constitutes a vital refractive component within the animal eye, comprised of the lens cortex and the lens nucleus. The cortex encompasses the periphery near the lens capsule, while the nucleus occupies the central region. Encasing the lens is a transparent and elastic lens capsule.

Under normal conditions, the lens is anchored by the suspensory ligament and rests directly posterior to the pupil, aligning closely with the visual axis. However, congenital dysplasia, trauma, or other pathologies can rupture the suspensory ligament, resulting in abnormal lens positioning and dislocation. Lens dislocation manifests in primary, secondary, and traumatic forms¹. Primary dislocation predominates in dogs, typically occurring before the age of 5 years. Certain terrier breeds exhibit a genetic predisposition², including Miniature Schnauzers, Shar-Peis, and Poodles, though the genetic mechanisms remain unconfirmed³. Fragility in the lens suspensory ligament structure renders it susceptible to rupture even from minor external forces. Secondary lens dislocation can stem from various factors such as blunt trauma, glaucoma, uveitis, intraocular tumors, or cataracts. Total lens dislocation is categorized as anterior or posterior based on its location. Anterior dislocation precipitates acute, intense pain, corneal edema, and glaucoma, necessitating urgent ophthalmic intervention. Conversely, posterior lens dislocation presents milder symptoms initially, characterized by anterior chamber deepening and posterior iris displacement, potentially progressing to complications like retinal detachment and glaucoma ⁴.

There exists no consensus regarding the management of lens subluxation and posterior dislocation. Some clinicians advocate for intracapsular lens extraction combined with vitrectomy to mitigate the risk of glaucoma. Conversely, others suggest utilizing mydriatic drugs in combination with other pharmacotherapy, especially in the absence of glaucoma. For anterior lens dislocation, intracapsular extraction or phacoemulsification stands as the preferred intervention. Notably, primary lens dislocation often presents bilaterally, necessitating preventative measures such as pupil constriction in unaffected eyes to avert anterior lens dislocation. Addressing the underlying cause is paramount in managing secondary lens dislocation, as mere symptomatic treatment yields limited efficacy⁵.

Cataract is a condition characterized by alterations in the transparency of the lens or lens capsule. The extent, severity, morphology, etiology, localization, and progression rate of lens opacification vary. Lens transparency preservation necessitates coordinated efforts of lens nutrition, energy metabolism, protein metabolism, and osmotic equilibrium. Disruptions in these factors result in irreversible alterations in lens protein composition, energy pumps, ion concentrations, and antioxidant activity, culminating in lens opacity ^6,7.

Various classification systems exist for cataracts. Based on developmental stages, cataracts are categorized into early, immature, mature, over-mature, and hard nucleus liquefaction cataracts⁸. According to age of onset, they are classified as congenital, juvenile, or senile cataracts. Furthermore, cataracts are classified by etiology into hereditary or acquired types, which include factors such as trauma, nutritional deficiencies, radiation exposure, secondary diabetes, poisoning, uveitis, glaucoma, retinopathy, congenital abnormalities, and aging⁹. Currently, no effective pharmaceutical intervention for treating canine cataracts is available on the market. Although topical aldose reductase inhibitor eye drops have shown some efficacy in inhibiting cataract formation in dogs, they have not been commercialized ¹⁰. Hence, surgical intervention remains the primary option for vision restoration¹¹. Phacoemulsification stands as the predominant surgical technique in contemporary practice.

However, in treating lens conditions such as lens dislocation and cataracts, animals often experience severe hyperopia after lens removal, significantly impacting their quality of life. To maximize visual acuity restoration, cataract surgery typically involves intraocular lens (IOL) implantation following phacoemulsification. The most prevalent method is intracapsular IOL (posterior chamber IOL) implantation. However, lens capsule rupture commonly complicates this procedure, rendering it unsuitable for highly mature cataracts, congenital abnormalities, inherent ocular diseases, aging-related changes, and severe ocular trauma cases where intracapsular IOL implantation is impractical due to damaged lens capsule and suspensory ligaments. Currently, the alternative approach involves posterior chamber IOL suspension¹². However, this technique is intricate and demands meticulous surgical skill. Moreover, it carries a heightened risk of severe complications such as intraocular hemorrhage, endophthalmitis, and retinal detachment ^13–15.

Currently, human medicine addresses this issue by offering alternatives to posterior chamber IOL suspension, including anterior chamber IOL implantation. This procedure is straightforward and associated with fewer intraoperative and postoperative complications^16,17. Two primary types of anterior chamber IOLs exist: elastic open-loop anterior chamber IOLs and iris-clip anterior chamber IOLs ^18,19. Comparatively, iris-clip anterior chamber IOLs have minimal impact on chamber angle, fixed positioning, and minimal corneal stimulation, making them an optimal choice for anterior chamber IOL implantation ^19–21.

This study aimed to assess the efficacy of iris clip anterior chamber IOL in improving visual acuity in dogs diagnosed with bilateral hereditary cataracts. The feasibility and clinical application value of this approach were analyzed, providing a scientific foundation for its use in treating canine aphakic eyes with iris clip anterior chamber IOLs.

2.1Experimental animals

Between 2017 and 2018, we collected a total of 12 dogs clinically diagnosed with hereditary cataracts in both eyes, primarily in the early or immature stages. Owners were engaged in extensive communication and negotiation, agreeing to relevant surgical tests and providing informed consent by signing consent forms.

The dogs, aged 2 to 6 years and weighing 4 to 10 kg, underwent thorough eye ultrasound, routine physical examination, blood routine examination, and serum biochemical examination prior to experimentation. No retinal abnormalities or other notable indexes were detected. Each dog's both eyes were divided into experimental and control groups. Phacoemulsification and lens removal were performed on both eyes, with intraocular lens implantation in one randomly selected eye of each dog.

Following surgery, the experimental dogs were monitored and treated for 3–4 months, while the control group underwent aphakic eye implantation again, with postoperative care extending for 3 months until complete recovery.

All expenses incurred, from diagnosis to full postoperative rehabilitation, were covered by our team.

2.2 Iris-clip anterior chamber intraocular lens

In this experiment, all eyes underwent implantation of human iris-clip aphakic intraocular lenses (Artisan, AMO, USA). These intraocular lenses are positioned in the anterior chamber and secured onto the anterior surface of the iris by gripping a portion of the iris through the lens loop's 'claw'. The lenses are constructed from polymethyl methacrylate (PMMA), providing a filtered ultraviolet wavelength of 400 nm and a visible spectral transmittance of 90%.

2.3 Routine eye examination

The routine examination of eyes was performed before operation, including:

(1) Pupil light reflection, threat reflection, dazzling reflection, tracer tracking reflection, maze test;

(2) Schirmer tear test (STT), intraocular pressure (IOP);

(3) Aqueous flare examination, corneal and iris examination, mydriasis for lens, vitreous and fundus examination.

2.4 Anesthesia

(1)Mydriatic Drugs: One percent atropine eye ointment was administered one day prior to surgery, every six hours, one drop per application.

(2)Pre-Anesthesia Administration: Zoletil 50 (a 1:1 mixture of zolazepam and tiletamine) was administered at a dose of 1 mg/kg, and dexmedetomidine at a dose of 75 µg/m², both via intramuscular injection.

(3)Anesthesia Induction: Following sedation, a venous indwelling needle was placed in the brachial vein, and propofol was administered intravenously at a dose of 2–5 mg/kg.

(4)Local Anesthesia: A retrobulbar block was achieved by injecting 1 ml of 0.5% bupivacaine into both eyes, while surface anesthesia was attained by applying 0.5% procaine to the ocular surface.

(5)Anesthesia Maintenance: General anesthesia was maintained through inhalation of isoflurane, adjusted according to the dog's condition and the surgical procedure. Normal saline was infused intravenously at a rate of 5–20 ml/kg/h, adjusted based on the dog's condition.

(6)Muscle Relaxant: Rocuronium bromide was administered intravenously as needed during the procedure at a dose of 0.25–0.5 mg/kg. Following administration of rocuronium bromide, artificial positive pressure ventilation was provided using a ventilator to assist breathing.

2.5 Operational methods

Prior to surgery, the animals underwent a 6-hour fasting period and a 2-hour water deprivation period. A physical examination was conducted to assess their general condition.

Following anesthesia, the eyelids and periocular hairs were trimmed, and the eyelids, corneas, and conjunctivas were cleansed with a 0.025% povidone iodine solution, followed by irrigation with sterile saline. The head was positioned and secured, and the eyelids were re-disinfected before draping with a surgical drape.

An incision of 1 cm was made at the outer canthus to expose the surgical area. Using a 3.2 mm corneal puncture knife, a puncture was made at the 12 o'clock position on the transparent limbus to access the anterior chamber, followed by injection of a viscoelastic agent. Capsulorhexis was performed, followed by ultrasonic emulsification and aspiration of the lens nucleus and cortex.

Pilocarpine was injected into the anterior chamber to induce miosis, and pilocarpine and latanoprost eye drops were administered to further reduce pupil size. The main incision was enlarged to 5.5 mm, with lateral incisions made at the 3 and 9 o'clock positions to facilitate implantation of the IOL. The IOL's long axis was oriented horizontally, and the iris was grasped and fixed using Artisan special clamping tweezers. The lens loops were anchored to the iris surface at the 3 o'clock and 9 o'clock positions, with approximately 1.5-2mm of iris tissue grasped, ensuring the optical center of the lens aligned with the pupil center. The iris root was incised at the 12 o'clock direction, with an incision diameter of 2 mm. Closure of the main and lateral incisions was achieved with 10/0 absorbable sutures. As the main incision neared closure, viscoelastic agent within the anterior chamber was aspirated. The outer canthus was sutured using 4/0 absorbable sutures. (Fig. 1)

Post-surgery, the experimental animals regained consciousness and were fitted with an Elizabethan collar.

2.6 Postoperative nursing

2.6.1 Postoperative medication

Tobradex eyedrops (tobramycin and dexamethasone eye drops) and diclofenac sodium eye drops, one drop at a time, each drug interval of 10 min, 4 times a day, administration for 3 weeks ; Synulox were taken orally, once a day, for 1 week.

2.6.2 Ophthalmic examination was performed within 3 weeks after surgery.

(1) The Schirmer tear test (STT), once a day

(2) Pupil light reflection, threat reflection, dazzling reflection, object tracking reflection, once a day

(3) The corneal morphology, IOL position, iris morphology, aqueous flare and other ocular appearance were observed by slit lamp once a day.

(4) Intraocular pressure (IOP) test, 4 times a day

2.6.3 Ophthalmic examination was performed within 3 weeks to 3 months after operation.

(1) The routine examination was the same as that within 3 weeks after operation, once a week.

(2) The maze test was performed on both eyes at 1 month, 2 months and 3 months after surgery. After anesthesia, the refractive power of the anterior chamber lens implanted eyes was detected by retinoscopy.

2.7 Statistical analysis.

Statistical analysis was conducted using SPSS software. Measurement data were presented as mean ± standard deviation (X ± S) following normality testing. Paired sample t-tests were employed for comparing measurement data, while ordinal data underwent non-parametric rank sum testing. Multiple datasets were analyzed using completely randomized design analysis of variance. A significance level of P < 0.05 was deemed statistically significant.

Statistical project composition: Intraocular pressure (IOP) ; The Schirmer tear test(STT); Corneal edema and aqueous flare grading(Table 1) and recovery time; Refractive power of lens implanted eye.

Table 1

Corneal hydrops and aqueous flare grading
Diagnostic	Grading	Clinical manifestation
Corneal hydrops	0	Corneal transparent without edema
	1	Corneal local misty edema, corneal endothelial surface smooth, still can see the clear iris texture.
	2	Corneal edema is light gray, the endothelial surface was rough, and the iris texture was blurred.
	3	Diffuse gray-white corneal edema, the inner surface of the crack-like, can't see the iris texture
	4	Corneal milky white edema, can't see the intraocular structure
Aqueous flare	0	There is no aqueous flare, and no light beam in the slit lamp light band through the area.
	1+	Weak aqueous flare, visible fuzzy beam of light
	2+	Moderate aqueous flare, visible slit lamp beam in the anterior chamber, can distinguish the iris and lens details.
	3+	Significant aqueous flare, obvious slit lamp beam in anterior chamber, inability to see iris and lens.
	4+	Serious aqueous flare, aqueous close to solidification, with a large number of fibrous exudates.

2.8 Statement

The experimental animals and methods used in this experiment were in accordance with the ARRIVE guidelines and regulations. This protocol complied with animal welfare standards and was approved by the Animal Ethics Committee of China Agricultural University (Approval ID: AW82304202-2-5).

3.1 Intraocular pressure (IOP)

The preoperative IOP of the experimental group was 14.49 ± 1.17 mmHg, and the IOP of the control group was 14.51 ± 1.01 mmHg. There was no significant difference between the two groups (Table 2). The IOP of the experimental group and the control group showed a gradual downward trend after operation (Fig. 2, Fig. 3). Postoperative IOP in the experimental group was lower than that in the control group, but the difference was statistically significant only on the 7th day after operation.

Because the IOP of the experimental group and the control group gradually decreased to a lower level after operation, conjunctival congestion occurred in some eyes of the experimental group and the control group. All the experimental groups and the control group began to take medicine on the same date 3 months after operation(S1). There was a statistically significant difference in IOP between the experimental group and the control group at the beginning of medication. After treatment, conjunctival congestion disappeared and intraocular pressure increased in the experimental group and the control group(S2). Gradually reduce the frequency of medication to diclofenac sodium eye drops once a day, intraocular pressure can be maintained stable.

Table 2

Comparison of IOP between the experimental group and the control group within 3 months after operation
Time	Experiment(mmHg)	Control(mmHg)	T-value	P-value
preoperation	14.49 ± 1.17	14.51 ± 1.01	0.136	0.894
12 hours	13.45 ± 2.53	14.64 ± 3.14	1.522	0.156
1 d	12.02 ± 2.20	12.41 ± 3.04	0.464	0.652
2 d	12.83 ± 1.35	13.54 ± 1.53	1.398	0.190
3 d	12.74 ± 0.83	12.89 ± 0.95	0.438	0.670
4 d	12.26 ± 1.56	13.21 ± 1.24	1.564	0.146
5 d	11.82 ± 0.95	12.91 ± 1.28	2.007	0.070
6 d	11.47 ± 1.29	12.37 ± 1.06	1.996	0.071
7 d	11.12 ± 1.31	12.17 ± 1.21	2.702	0.021
14 d	11.20 ± 1.38	12.15 ± 1.48	1.474	0.169
21 d	11.25 ± 1.29	11.49 ± 1.21	0.584	0.571
30 d	11.05 ± 1.22	11.15 ± 1.83	0.197	0.847
60 d	9.83 ± 1.13	10.06 ± 1.22	0.971	0.353
90 d	8.96 ± 1.53	9.28 ± 1.28	1.133	0.281

3.2 The Schirmer tear test (STT)

Before surgery, the results of STT in the experimental group were 17.67 ± 1.56, and the STT in the control group was 17.50 ± 1.45. There was no significant difference between the two groups. One day after operation, the STT of the experimental group and the control group was lower than that before operation, and the difference was statistically significant. From 2 days to 45 days after operation, the STT of the experimental group and the control group showed a trend of decreasing first and then increasing. The measured value was the lowest on the 14th day after operation, the experimental group was 13.75 ± 2.45, and the control group was 16.25 ± 2.83. From 4 days to 21 days after operation, the STT of the experimental group was lower than the normal value ( STT<15 ). After 37 days, the STT of the experimental group returned to normal ( 15 ≤ STT ≤ 20 ) ( Table 3, Fig. 4 ).

Table 3

Comparison of STT between the experimental group and the control group within 45 days after operation
Time	Experiment	Control	T-value	P-value
preoperation	17.67 ± 1.56	17.50 ± 1.45	0.290	0.777
1 d	14.75 ± 3.49	14.50 ± 2.32	0.208	0.839
2 d	18.17 ± 3.35	18.42 ± 3.15	0.279	0.786
3 d	16.42 ± 3.99	16.33 ± 2.77	0.064	0.950
4 d	14.50 ± 3.53	16.17 ± 1.75	2.246	0.046
5 d	15.00 ± 2.52	16.33 ± 1.73	1.797	0.100
6 d	14.83 ± 2.69	16.75 ± 2.56	2.653	0.022
7 d	14.58 ± 2.11	16.67 ± 2.31	2.661	0.022
14 d	13.75 ± 2.45	16.25 ± 2.83	3.409	0.006
21 d	14.00 ± 2.22	17.25 ± 1.36	5.166	0.000
30 d	15.33 ± 2.53	17.75 ± 1.54	2.613	0.024
37 d	17.08 ± 1.83	18.08 ± 1.73	1.414	0.185
45 d	17.50 ± 1.78	18.00 ± 1.48	0.856	0.410

3.3 Corneal hydrops

No corneal edema was observed in any of the eyes in both the experimental and control groups before surgery. After surgery, 100% (12/12) of the experimental group and 83% (10/12) of the control group had different degrees of corneal edema (S3). Corneal edema grading and recovery time are shown in Table 4, Fig. 5 and Fig. 6. The median degree of corneal edema in the experimental group was 2, and the most severe degree of corneal edema was grade 3. The median degree of corneal edema in the control group was 1, and the most severe degree of corneal edema was grade 2. The difference was statistically significant (z = 3.066, P = 0.002). The average recovery time of corneal edema in the experimental group was 13.08 ± 15.80 days, and the longest recovery time was 60 days. The average recovery time of corneal edema in the control group was 2.67 ± 2.10 days, and the longest recovery time was 7 days. The difference was statistically significant (z = 3.065, P = 0.002).

Table 4

Comparison of corneal edema grading and recovery time between the experimental group and the control group
Corneal hydrops(grade)	Experiment		Control
Corneal hydrops(grade)	number of samples	The average recovery time (days)	number of samples	The average recovery time (days)
0	0	/	2	0
1	1	3.0	7	2.3
2	6	5.5	3	5.3
3	5	24.6	0	/
4	0	/	0	/

3.4 Aqueous flare

Prior to surgery, there was no aqueous flare observed in the eyes of both the experimental and control groups. Different degrees of aqueous flare appeared in 100% (12/12) experimental group and 92% (11/12) control group after operation. The degree of aqueous flare and recovery time are shown in Table 5 and Fig. 7. The median degree of aqueous flare in the experimental group was 3, and the median degree of aqueous flare in the control group was 2. The difference was statistically significant (z = 2.640, P = 0.008). The average disappearance time of aqueous flare in the experimental group was 7.75 ± 3.91 days, and the average disappearance time of aqueous flare in the control group was 4.75 ± 3.08 days. The difference was statistically significant (z = 2.956, P = 0.003). After the aqueous flare disappeared, there was no aqueous flare in the experimental group and the control group.

Table 5

Comparison of aqueous flare grading and recovery time between the experimental group and the control group
Aqueous flare (grade)	Experiment		Control
Aqueous flare (grade)	number of samples	Average disappearance time (days)	number of samples	Average disappearance time (days)
0	0	/	1	0
1+	2	2.0	4	3.0
2+	6	7.3	6	5.3
3+	7	9.6	1	12
4+	0	/	0	/

3.5 Other ocular symptoms

Both the experimental and control groups exhibited varying degrees of conjunctival congestion post-surgery, which resolved within 4–7 days. There was no significant disparity observed in either the degree of congestion or the duration of recovery between the groups. However, after 3 weeks of discontinuing medication, mild to moderate conjunctival congestion reappeared in 10 eyes of the experimental group and 7 eyes of the control group. Notably, the experimental group displayed more pronounced congestion compared to the control group, although this resolved after resuming medication.

In the experimental group, two eyes and in the control group, three eyes exhibited postoperative anterior chamber fiber deposition, which was absorbed within approximately 6 weeks (S4).

One eye in the experimental group experienced iris root incision bleeding, hyphema, and corneal edema 2 days after surgery, graded at 3 + severity (S5). The incision bleeding ceased spontaneously without intervention and resolved completely within 5 days. Due to iris root incision contraction, the pupil and implanted IOL shifted upward by approximately 1 mm compared to their intraoperative positions. Despite this, the IOL loop remained stable without loosening.

Following surgery, iris pigmentation spots were observed in three eyes of the experimental group and one eye of the control group. Additionally, postoperative adhesion between the iris and residual lens capsule occurred in one eye from each group, resulting in pupil deformation, which resolved within 2 weeks post-surgery.

Two days after the procedure, fiber formation within the lens capsule was evident in both the experimental and control groups, primarily concentrated around the anterior capsule pocket. Moreover, cellulose formation in the posterior capsule of the lens was noted in two eyes of each group.

Postoperative vitreous and fundus examinations revealed no abnormalities in either group.

3.6 vision

The dazzle reflex of both the experimental and control groups was positive one day post-operation. In the experimental group, five eyes displayed a weak threat reflex one day after surgery, due to aqueous flare or severe corneal edema, which became pronounced 3–10 days post-operation. The remaining threat reflexes were positive one day post-surgery.

Eight eyes in the experimental group and all eyes in the control group exhibited a tracer reaction 2–4 days post-surgery. Among the experimental group, four eyes with aqueous flare or severe corneal edema showed a tracer reaction 6–10 days post-surgery. Two months post-operation, testing with a 5 cm diameter object revealed obvious reactions from both the experimental and control groups when the object moved 50 cm away from the eye. At 30 cm distance, three control eyes and all experimental eyes showed obvious reactions, while other control eyes exhibited weak reactions. When the object approached 15 cm from the eye, eight eyes in the experimental group displayed obvious reactions, four eyes showed weak reactions, and the control group demonstrated weak or no reactions.

The maze test administered at different intervals post-operation was successfully completed by both the experimental and control groups, with no discernible differences between them.

The refractive power of eyes in the experimental group measured 2.58 ± 0.99 D, 2.50 ± 1.19 D, and 2.66 ± 1.02 D at 1 month, 2 months, and 3 months post-surgery, respectively. Statistical analysis revealed no significant differences (F = 0.72, P = 0.930).

Hereditary cataract results from mutations in the gene encoding crystallin proteins, leading to structural and functional abnormalities in the lens, impairing its transparency and causing cataracts. Symptoms are typically noticeable during youth, when the cataract is in its early or immature stages, presenting an optimal window for phacoemulsification, characterized by fewer postoperative complications and quicker recovery. This study aims to collect clinically diagnosed cases of hereditary cataract as experimental subjects. Doing so not only minimizes the influence of preoperative corneal edema and aqueous flare on postoperative evaluation but also reduces complications stemming from factors unrelated to the surgery itself. This approach enables a more accurate assessment of the surgery's impact on canine eyes and evaluates the feasibility of the surgical method to its fullest extent.

Several factors contribute to increased intraocular pressure post-operation, including residue of viscoelastic agents, inflammation, obstruction of trabecular meshwork by red blood cells, and accumulation of small molecules and macromolecular proteins due to intraocular trauma. Other causes may involve trabecular meshwork edema and residue of lens debris ^22,23. Elevated intraocular pressure can lead to pain and corneal edema, and prolonged elevation may result in nerve damage^24,25. Furthermore, iris-clip anterior chamber IOL surgery can lead to various complications, such as corneal edema and aqueous flare, in addition to altering intraocular pressure and tear secretion. This study systematically examines these complications, their etiology, and prognosis to elucidate the safety profile of this surgery and enhance its applicability in dogs with aphakic eyes.

In this study, both experimental and control groups exhibited a transient increase in IOP. Following a single application of brinzolamide eye drops, IOP decreased and remained stable thereafter. This rise in IOP occurred within 2 weeks post-surgery, likely due to surgical trauma and residual lens debris triggering an inflammatory response. This inflammation disrupted the blood-aqueous barrier, leading to protein exudation, trabecular meshwork blockage, and compromised aqueous humor outflow, culminating in elevated intraocular pressure ⁶. In one experimental group, iris root incision bleeding occurred on the second postoperative day, coinciding with severe inflammatory response and weakened IOP regulation. Additionally, external noise-induced panic in one dog exacerbated the situation. The control group also experienced a simultaneous IOP increase, peaking at 22 mmHg. Analysis suggests stress as the primary contributor to elevated intraocular pressure.

Two weeks post-operation, neither the experimental nor the control group exhibited elevated IOP. By the third week of follow-up, IOP gradually declined in both groups, with some eyes displaying conjunctival congestion. At the three-month mark post-operation, the average IOP in both groups was below 10 mmHg. Ocular hypotension analysis suggests two main factors: First, lens removal disrupted the anterior chamber's structural support, leading to chamber deepening and increased space, coupled with inadequate aqueous humor production to maintain normal IOP. Second, chronic iridocyclitis post-surgery reduced aqueous humor production, while inflammation-induced prostaglandin release enhanced aqueous humor outflow, contributing to lowered IOP ²⁶. Upon resuming anti-inflammatory treatment, average IOP in both groups rose above 10 mmHg, accompanied by resolution of conjunctival congestion, confirming inflammation's role in reducing IOP in both experimental and control groups.

IOP in the experimental group was observed to be lower compared to the control group post-operation. This disparity could potentially be attributed to the stimulation of the iris by the implanted anterior chamber IOL. Besides, the IOL implantation procedure itself might have caused damage to the iris. Notably, the human IOL used in this study had dimensions mismatched to those of canine irises, potentially leading to increased stimulation and exacerbation of postoperative anterior uveitis. By the seventh day following surgery, the combined effects of anti-inflammatory medication and self-repair mechanisms had resulted in varying degrees of reduction in inflammation and anterior uveitis. Consequently, the reduction in aqueous humor varied accordingly, with more pronounced effects observed during this period. Continued use of anti-inflammatory drugs subsequently mitigated inflammation, resulting in a diminishing disparity between the experimental and control groups. However, upon cessation of medication, chronic inflammation ensued in both groups, with the IOL stimulation intensifying inflammation slightly more in the experimental group than in the control group. Consequently, a significant difference in IOP between the two groups re-emerged before the second round of medication. Following the administration of anti-inflammatory treatment to manage inflammation, the IOP of both groups rebounded, and the difference attributed to inflammation also diminished.

Similarly, the comparative analysis of aqueous flare in both the experimental and control groups suggested a consistent inflammatory response process. Aqueous flare serves as a diagnostic indicator of anterior uveitis, wherein a higher degree of flare signifies a more severe inflammatory reaction. However, the absence of aqueous flare does not conclusively negate the presence of anterior uveitis. Following the surgical procedures, varying degrees of aqueous flare were observed in both groups. Notably, the experimental group exhibited more pronounced aqueous flare and a prolonged recovery period compared to the control group, indicating significant inflammation in the early postoperative stage. The resolution of aqueous flare without recurrence post-medication suggests the subsidence of inflammation, with subsequent mild inflammation following drug withdrawal. Throughout the maintenance period of the second medication, topical administration of non-steroidal anti-inflammatory drugs once daily was employed. The mean IOP remained within the normal range, and no additional symptoms manifested. These findings indicate that the inflammatory response induced by IOL implantation is mild and can be effectively managed through long-term medication.

The results of the tear secretion test indicated that the STT values of both the experimental and control groups were lower on the first day post-operation compared to pre-operation levels. However, by the second day post-operation, the STT values significantly increased, surpassing pre-operation levels. Subsequently, a gradual decline in STT values was observed, reaching the lowest point on the 14th day post-operation. Thereafter, a slow recovery ensued, with STT values stabilizing within the normal range by days 37 to 45 post-operation. This decline in STT following phacoemulsification correlates with reduced corneal sensitivity ²⁷. The surgical procedure involves cutting off a portion of the corneal nerve trunk, thereby diminishing corneal sensitivity and blink reflex. Additionally, the surgical incision at the limbus of the cornea, expanded from 3.2 mm to 5.5 mm, and the requisite lateral incision exacerbate nerve injury and decrease corneal sensitivity²⁸. The use of proparacaine during topical anesthesia and postoperative IOP examinations further affects corneal sensitivity. Other potential factors contributing to postoperative STT reduction include corneal damage from phacoemulsification, intraoperative corneal exposure, and direct instrument-induced corneal trauma²⁹. While some argue that topical medications may influence corneal sensitivity, studies suggest otherwise, with glucocorticoids showing no direct association with decreased corneal sensitivity even after a two-month cessation period ^27,30. Notably, in this study, the STT was lower one day post-surgery, possibly due to increased sticky secretions post-operation, thereby affecting STT test accuracy.

Corneal edema is a prevalent complication following phacoemulsification, with studies indicating an incidence rate as high as 87.39% within one day post-surgery ³¹. In our study, corneal edema was observed in all cases (100%) of the experimental group and in 83% of the control group. Notably, the severity of corneal edema was more pronounced in the experimental group compared to the control, with a longer average recovery time (S6). Maintaining corneal transparency relies heavily on the barrier function of the corneal epithelium and the normal metabolic activity of corneal endothelial cells. Various factors contribute to corneal edema during phacoemulsification, including local incision injury, where smaller incisions are associated with reduced corneal trauma and lower incidence of postoperative edema³². Mechanical stimulation of the cornea and endothelial cells by ultrasonic emulsification probes and lens debris splashing during surgery further exacerbate the risk of corneal edema. Additionally, the longer corneal incisions and the placement of anterior chamber intraocular lenses in the experimental group increased endothelial cell damage, resulting in more severe edema and longer recovery times ³³. Other factors contributing to corneal edema include the energy and duration of phacoemulsification, thermal burns from ultrasound, chemical damage from instrument disinfectants, viscoelastic agents, and irrigation fluids. Furthermore, anterior uveitis, which was more severe in the experimental group, can also induce corneal endothelial damage and exacerbate corneal edema. Acute elevation of intraocular pressure, as observed in one eye of the experimental group, can lead to significant corneal endothelial cell damage, accompanied by a notable increase in corneal edema.

Conjunctival edema and congestion are prevalent postoperative complications. Edema occurs due to eyelid opening and conjunctival manipulation during surgery, typically resolving within 1–2 days without lasting effects. Congestion, a nonspecific ophthalmological symptom, commonly manifests postoperatively. Various factors, including surgical manipulation, uveitis, and postoperative discomfort, contribute to conjunctival congestion in both experimental and control groups. Removal of irritants leads to resolution of conjunctival congestion ⁶.

Additionally, one eye in the experimental group experienced iris root incision bleeding 2 days post-operation, resulting in anterior chamber hemorrhage and corneal edema. This incident might be attributed to the animal's resistance during eye drop administration and IOP measurement, leading to struggle and emotional agitation, thus causing iris root incision bleeding. Compared to human irises, canine irises are thicker, making iris root resection-induced damage more significant, resulting in more pronounced scarring and slight pupil and IOL displacement. However, as long as the IOL aligns with the pupil, it will not substantially impact vision. Post-surgery, the position of the IOL loop remained fixed, without detachment, indicating that clamping an appropriate amount of iris tissue (1.5-2 mm) by the IOL loop firmly secures it to the iris surface, reducing the risk of detachment. Iris surface pigmentation, a sign of iritis, does not impair iris function. Adhesions between the iris and lens capsule arise from inflammatory exudates, resolving spontaneously with timely inflammation management. Fibrosis occurred in the anterior and posterior lens capsules but was limited. Visual acuity examination results indicated that fibrosis did not compromise postoperative visual acuity.

In the immediate postoperative phase, some dogs in the experimental group exhibited weakened visual reflexes due to corneal edema and turbidity of the aqueous humor. However, as the corneal edema and aqueous humor turbidity diminished, all dogs in both the experimental and control groups displayed positive basic visual reflexes. During assessments of dazzling reflex, threat reflex, and maze test, both experimental and control group dogs exhibited comparable performance, suggesting that aphakic canines possess sufficient vision to engage in daily activities with minimal visual demands. Notably, in the object tracking test, the experimental group outperformed the control group, particularly in perceiving closer objects. This disparity arises from the severe hyperopia characteristic of aphakic eyes, impairing their ability to focus on nearby objects.

The implanted anterior chamber IOL has a refractive power of 30D and is positioned approximately 2 mm from the original lens's optical center. Utilizing the formula D = 1/f (where D is the refractive power and f is the focal length), we determine that 1/30 = 1/D1 + 0.002, yielding an equivalent lens refractive power of 32D at the original lens position D1. The refractive power of a healthy canine lens typically measures around 41D. Aphakic eyes were assessed using the retinoscopy method, revealing a refractive power of approximately + 15D. Following the implantation of a 30D anterior chamber IOL, the refractive power of the eye stabilized at + 3.2D. Subsequent monthly measurements in the experimental group yielded refractive powers of 2.58 ± 0.99D, 2.50 ± 1.19D, and 2.66 ± 1.02D, respectively, post-operation, with no statistically significant differences observed. These recorded values are slightly lower than the anticipated theoretical values. This deviation may stem from calculation errors or the predominantly small size of the dogs used in the study. Small dogs typically exhibit a stronger corneal refractive power, contributing to an overall increase in ocular refractive power. As a result, their average refractive power is often negative, indicative of myopia during normal assessments ³⁴.

There is a paucity of studies investigating the use of iris-clip anterior chamber lens implantation for treating aphakic eyes in dogs. This study aims to assess the biocompatibility of human anterior chamber lenses in dogs and the feasibility of this procedure for treating aphakic eyes. By analyzing indicators such as IOP, STT, corneal edema, and aqueous flare, we sought to evaluate the efficacy of this approach. Preliminary findings suggest that the surgical technique and intraocular lens material meet the requirements for treating aphakic eyes in dogs. Moreover, it presents a novel alternative for cases where lens implantation within the capsule is not feasible, such as in cases of capsule rupture. However, to facilitate the widespread adoption of this surgical method, comprehensive data collection on its application for various lens diseases is imperative to assess safety thoroughly. Additionally, gathering data across diverse canine populations in terms of species, body size, and age is essential to enhance and advance the development of canine iris-clip intraocular lenses, thus refining the surgical approach and promoting its broader clinical application.

The implantation of iris-clip anterior chamber intraocular lenses may lead to complications such as elevated IOP, reduced STT, corneal edema, and anterior uveitis during the early postoperative phase. However, with localized drug therapy, these issues can be resolved, resulting in restored ocular function and significantly improved visual acuity in dogs. This confirms the feasibility of employing this surgical approach for treating aphakic eyes in canines.

Ethics approval and consent to participate

This protocol complied with animal welfare standards and was approved by the Animal Ethics Committee of China Agricultural University (Approval ID: AW82304202-2-5).

Consent for publication

Written informed consent for publication was obtained from all participants.

Availability of data and material

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Competing interests

The authors declare that they have no competing interests.

Funding

None

Authors' contributions

Yipeng Jin contributed to the conception of the study. Yuanheng Wu, Ying Liu and Yi Dong performed the experiment. Yuanheng Wu and Zichen Liu contributed significantly to analysis and manuscript preparation. Yuanheng Wu and Yang Bai performed the data analyses and wrote the manuscript. Yipeng Jin helped perform the analysis with constructive discussions. All authors contributed to the article and approved the submitted version.

Acknowledgments

I would like to give my heartfelt thanks to my supervisor, Professor Jin, for his kindness, illuminating guidance and experimental guidance.

The study was supported by the College of Veterinary Medicine at China Agricultural University.

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No competing interests reported.

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The Application Research on Iris-clip intraocular lens implantation for Aphakia in Canine

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Abstract

Objective

Method

Results

Conclusion

Figures

1. Introduction

2. Method and Materials

2.1Experimental animals

2.2 Iris-clip anterior chamber intraocular lens

2.3 Routine eye examination

2.4 Anesthesia

2.5 Operational methods

2.6 Postoperative nursing

2.6.1 Postoperative medication

2.6.2 Ophthalmic examination was performed within 3 weeks after surgery.

2.6.3 Ophthalmic examination was performed within 3 weeks to 3 months after operation.

2.7 Statistical analysis.

2.8 Statement

3. Results

3.1 Intraocular pressure (IOP)

3.2 The Schirmer tear test (STT)

3.3 Corneal hydrops

3.4 Aqueous flare

3.5 Other ocular symptoms

3.6 vision

4. Discussion

5. conclusion

Declarations

References

Additional Declarations

Supplementary Files

Status:

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