Ocular Pathology and Occasionally Detectable Intraocular Severe Acute Respiratory Syndrome Coronavirus-2 RNA in Five Fatal Coronavirus Disease-19 Cases.

INTRODUCTION: In December 2019, the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic broke out. The virus rapidly spread globally, resulting in a major world public-health crisis. The major disease manifestation occurs in the respiratory tract. However, further studies documented other systemic involvement. This study investigates histopathologic eye changes in postmortem material of coronavirus disease 2019 (COVID-19) patients. METHODS: Sections of formalin-fixed, paraffin-embedded eyes from 5 patients (10 eyes) who died of COVID-19 at the University Hospital in Basel were included. Gross examination and histological evaluation were performed by 3 independent ophthalmopathologists. Immunohistochemical staining was performed using antibodies against fibrin, cleaved caspase 3, and ACE-2. Five enucleated eyes of patients not infected with SARS-CoV-2 served as control group. All cases have been studied for presence of SARS-CoV-2 RNA by means of reverse transcription PCR and RNA in situ hybridization (ISH). The choroidal vessels of one case were analyzed with electron microscope. RESULTS: Ophthalmopathologically, 8 eyes from 4 patients displayed swollen endothelial cells in congested choroidal vessels. No further evidence of specific eye involvement of SARS-CoV-2 was found in any of the patients. In the 8 eyes with evidence of changes due to SARS-CoV-2, immunohistochemical staining demonstrated fibrin microthrombi, apoptotic changes of endothelial and inflammatory cells. In control eyes, ACE-2 was detectable in the conjunctiva, cornea, retina, and choroidea and displayed significantly lower amounts of stained cells as in COVID-19 eyes. SARS-CoV-2 RNA was detectable in both bulbi of 2/5 patients, yet ISH failed to visualize viruses. Electron microscopy showed no significant results due to the artifacts. DISCUSSION/CONCLUSION: As already described in other organs of COVID-19 patients, the ophthalmological examination revealed-microthrombi, that is, hypercoagulation and vasculopathy most probably due to endothelial damage. A possible viral spread to the endothelial cells via ACE-2 provides one pathophysiological explanation. The expression of ACE-2 receptors in the conjunctiva hints toward its susceptibility to infection. To what extend eyes, function is disrupted by SARS-CoV-2 is subject to further studies, especially in the clinic.

Contrast-enhanced ultrasonography for evaluation of blood perfusion in normal canine eyes.

OBJECTIVE: This study was performed to evaluate ocular structures using contrast-enhanced ultrasonography (CEUS) in dogs to assess the feasibility of CEUS for investigating the blood perfusion of canine eyes. ANIMAL STUDIED: Eight purpose-bred beagles were used. PROCEDURES: Blood perfusion and vascularity of the right eye were evaluated using color Doppler, power Doppler, and CEUS with Sonazoid® . Vascular changes were quantitatively evaluated by measuring peak intensity, time to initial upslope, and time to peak from the ciliary body, iris, choroid, retina, and the retrobulbar region by CEUS. RESULTS: On CEUS images, all parts of the examined ocular structures were markedly enhanced and clearly identified from the adjacent region. After injection, the contrast agent initially flowed to the choroid and retina at 14.2 seconds, then to the ciliary body and iris at 20 seconds. The blood signal reached its peak intensity in the ciliary body at 27.2 seconds (47.4 ± 10.63), in the iris at 31.6 seconds (74.00 ± 41.85), and in the retrobulbar region at 23.4 seconds (149 ± 24.59). The optic nerve was clearly distinguished from the retrobulbar region over 5 minutes after the initiation of CEUS. Significantly, more vascular signals were detected in the ciliary body and iris by CEUS than by color and power Doppler. CONCLUSION: Blood perfusion of the intraocular structures and the retrobulbar region can be quantitatively and qualitatively analyzed by CEUS. CEUS may be a useful, noninvasive, and sensitive tool for the evaluation of blood perfusion in ocular diseases.

Cilioretinal artery occlusion and anterior ischemic optic neuropathy as the initial presentation in a child female carrier of Fabry disease.

PURPOSE: To report the youngest female carrier of Fabry disease, complicated by cilioretinal artery occlusion and anterior ischemic optic neuropathy (AION). METHODS: Case report. RESULTS: An 11-year-old girl was referred to our clinic with painless, acute loss of vision in her right eye. Posterior segment examination and fluorescein angiography revealed cilioretinal artery occlusion and AION. Systemic evaluations were unremarkable, except for a low blood α-galactosidase A enzyme level of 242.27 pmol/spot*20 h (reference range: 450-2000 pmol/spot*20 h). The patient was diagnosed with female carrier of Fabry disease. CONCLUSION: Retinal vascular occlusions are rare in childhood, and Fabry disease may present with retinal vascular occlusion. Ophthalmological examinations may be contributing for early detection of the disease. To the best of our knowledge, this is the first report of a child female carrier of Fabry disease, complicated by cilioretinal artery occlusion and AION.

Radiation induced violations of blood circulation in the ciliary body and changes of the anterior chamber angle in the pathogenesis of glaucoma in clean up workers of the Chornobyl NPP accident and residents of contaminated areas. / RADITsIY̆NO INDUKOVANI PORUShENNIa KROVOOBIGU V TsILIARNOMU TILI TA ZMINY KUTA PEREDN'OI KAMERY OKA V PATOGENEZI GLAUKOMY V UChASNYKIV AVARIY̆NYKh ROBIT NA ChORNOBYL'S'KIY̆ AES I MEShKANTsIV ZABRUDNENYKh TERYTORIY̆.

OBJECTIVE: Estimate changes blood filling of the ciliary body and changes of the anterior chamber angle; study their influence to glaucoma pathogenesis in irradiated persons. MATERIALS AND METHODS: Used the results of a randomly selected group survey of 41 clean up workers of the Chornobyl NPP accident (clean up workers), and 18 inhabitants of the zone of guaranteed voluntary resettlement; age at the time of the survey was 45-50 years. The control group consisted of 41 persons of the same age had not radiation exposure. State of the anterior chamber angle studied by gonioscopy, which was conducted 35 clean up workers and 35 persons of the control group. Changes of the blood circulation in the ciliary body examine by the ophtalmoreog raphy, what was done on 12 eyes of 6 clean up workers, control was 12 eyes of 6 persons had not radiation exposure. RESULTS: Detection revealed of the blood circulation in the ciliary body in all clean up workers, reography coefficient was probably lower (p < 0.05), than in the control group. The research of the state of the anterior chamber angle revealed a higher relative risk of appearance of involution changes of the anterior chamber angle in clean up work ers of ChNPP accident, in comparison with the control group was 3.5 (1.27; 9.5) χ2 = 7.48, p = 0.031. The same changes are characteristic for inhabitants of radiation polluted territories. CONCLUSIONS: Influence ionizing radiation causes a blood circulation decrease in the ciliary body and development changes of the angle of the anterior chamber. Presence of these changes can explain the features of the pathogene sis of glaucoma in irradiated late manifestation and, at the same time, severe course.

Evaluation of ocular pulse amplitude in non-arteritic anterior ischaemic optic neuropathy.

BACKGROUND: To evaluate the ocular pulse amplitude (OPA) in patients with chronic non-arteritic anterior ischaemic optic neuropathy (NAION). METHODS: This cross-sectional study comprised a study group of 30 eyes from 30 patients with NAION and a control group of 31 eyes from 31 age and gender-matched healthy subjects. Bilateral OPA was measured with dynamic contour tonometry (DCT) and was compared between the study and control groups. RESULTS: No statistically significant difference was found between the study and control groups in terms of hypertension, diabetes mellitus, ischaemic heart disease and hyperlipidemia. The mean intraocular pressure (IOP) measured with Goldmann Applanation Tonometry and DCT in the study and control groups was not statistically different (p1 = 0.094, p2 = 0.240). The mean OPA in the study group and the control group were 2.01 ± 0.69 mmHg and 1.97 ± 0.68 mmHg (p = 0.839). CONCLUSION: No significant difference was determined in the OPA levels of eyes with NAION at the chronic stage and eyes in the control group.

Microvasculature of the California sea lion (Zalophus californianus) eye and its functional significance.

OBJECTIVE: To examine the ocular circulation in California sea lions (Zalophus californianus). ANIMALS STUDIED: Eyes were obtained postmortem from three sea lions that died while in captivity. PROCEDURES: Specimens from sea lions were investigated using scanning electron microscopy (SEM) of vascular corrosion casts. The thermal characteristics of live animal eyes were measured using an infrared imaging system. RESULTS: The major orbital artery of the sea lion was the ophthalmic artery. The artery was remarkably thick in diameter, showed a marked convolution and formed an ophthalmic rete around the optic nerve at the posterior pole of the eyeball. The long posterior ciliary artery terminates to form a prominent inner arterial circle at the pupillary margin. The iridial arteries originated from the arterial circle showing either a crimped or somewhat coiled course, extending toward the root of the iris and formed a root supplying a large amount of blood to the iris and ciliary bodies. The venules in the conjunctiva formed a well-developed venous plexus. The vortex veins showed a dilation and constriction at the site passing through the sclera. Thermographic examination revealed that the eye showed a higher degree of thermal emission than adjacent skin areas. CONCLUSIONS: These characteristics suggest that the ocular vasculature might play roles in thermoregulation as well as in hemodynamics by draining a large amount of blood so that the appropriate operating temperature for the eye can be maintained in a deep and cold aquatic environment.

The effects of VEGF-A-inhibitors aflibercept and ranibizumab on the ciliary body and iris of monkeys.

PURPOSE: To investigate the effects of intravitreal ranibizumab (Lucentis®) and aflibercept (Eylea®) on the ciliary body and the iris of 12 cynomolgus monkeys with regard to the fenestrations of their blood vessels. MATERIALS AND METHODS: Structural changes in the ciliary body and in the iris were investigated with light, fluorescent, and transmission electron microscopy (TEM). The latter was used to specifically quantify fenestrations of the endothelium of blood vessels after treatment with aflibercept and ranibizumab. Each of the two ciliary bodies treated with aflibercept and the two treated with ranibizumab and their controls were examined after 1 and 7 days respectively. Ophthalmological investigations including funduscopy and intraocular pressure measurements were also applied. RESULTS: Ophthalmological investigations did not reveal any changes within the groups. Both drugs reduced the VEGF concentration in the ciliary body pigmented epithelium. The structure of the ciliary body was not influenced, while the posterior pigmented epithelium of the iris showed vacuoles after aflibercept treatment. Ranibizumab was mainly concentrated on the surface layer of the ciliary epithelium, in the blood vessel walls and the lumen of some of the blood vessels, and in the cells of the epithelium of the ciliary body. Aflibercept was more concentrated in the stroma and not in the cells of the epithelium, but as with ranibizumab, also in the blood vessel walls and some of their lumina, and again on the surface layer of the epithelium. Both aflibercept-and ranibizumab-treated eyes showed a decreased number of fenestrations of the capillaries in the ciliary body compared to the untreated controls. On day 1 and day 7, aflibercept had fewer fenestrations than the ranibizumab samples of the same day. CONCLUSIONS: Both aflibercept and ranibizumab were found to reach the blood vessel walls of the ciliary body, and effectively reduced their fenestrations. Aflibercept might eliminate VEGF to a greater extent, possibly due to a higher elimination of fenestrations in a shorter time. Moreover, the vacuoles found in the iris need further research, in order to evaluate whether they carry a possible pathological potential.

Functional Anatomy of the Outflow Facilities.

In order to understand the pathophysiology, select optimal therapeutic options for patients and provide clients with honest expectations for cases of canine glaucoma, clinicians should be familiar with a rational understanding of the functional anatomy of the ocular structures involved in this group of diseases. The topographical extension and the structural and humoral complexity of the regions involved with the production and the outflow of aqueous humor undergo numerous changes with aging and disease. Therefore, the anatomy relative to the fluid dynamics of aqueous has become a pivotal yet flexible concept to interpret the different phenotypes of glaucoma.

Topography of Lymphatic Markers in Human Iris and Ciliary Body.

PURPOSE: Reports of lymphatics in the anterior human uvea are contradictory. This might be caused due to a certain topography, which has not been considered yet. Therefore, here we systematically analyze iris and adjacent ciliary body with immunohistochemistry by combining various lymphatic markers. METHODS: Human iris and ciliary body were obtained from cornea donors and prepared for cryosectioning. Cross sections of tissue blocks at 12/3/6/9 o'clock position and at corresponding intersections (1:30/4:30/7:30/10:30) were processed for immunohistochemistry of LYVE-1, PDPN, PROX1, FOXC2, VEGFR3, and CCL21, and when necessary, these lymphatic markers were combined with CD31, α-smooth muscle-actin, CD68, and 4',6-diamidino-2 phenylindole dihydrochloride (DAPI). Double, triple, and quadruple marker combinations were documented using confocal microscopy. RESULTS: Numerous podoplanin+ cells were mainly located at the anterior border of the iris while LYVE-1+ cells were distributed throughout the nonpigmented part. Both cell populations were PROX1/FOXC2/CCL21/VEGFR3-. Blood vessels, iris smooth muscles, and individual cells were VEGFR3+. While PDPN+ cells were rarely detected posteriorly of the iris root, many LYVE-1+ cells were present within the ciliary body muscle and villi. Within the muscle, occasionally PDPN+ vessel-like structures were detectable, but these were never colocalized with LYVE-1. Similar vessel-like structures were VEGFR3+/PROX1-/CCL21-, but CD31+. Further, ciliary muscle fibers and ciliary epithelium were immunoreactive for VEGFR3/CCL21, but were LYVE-1/PDPN-. A certain topography of structures at the various uvea-positions investigated was not obvious. The majority of LYVE-1+ cells displayed immunoreactivity for CD68. CONCLUSIONS: Lymphatic vessels colocalizing for at least two lymphatic markers were not detectable. Therefore, if present, putative lymphatic channels of the anterior uvea might display a different marker panel than generally presumed.

Photoacoustic tomography imaging and estimation of oxygen saturation of hemoglobin in ocular tissue of rabbits.

This study evaluated in vivo imaging capabilities and safety of qualitative monitoring of oxygen saturation of hemoglobin (sO2) of rabbit ciliary body tissues obtained with acoustic resolution (AR) photoacoustic tomography (PAT). AR PAT was used to collect trans-scleral images from ciliary body vasculature of seven New Zealand White rabbits. The PAT sO2 measurements were obtained under the following conditions: when systemic sO2 as measured by pulse oximetry was between 100% and 99% (level 1); systemic sO2 as measured by pulse oximetry was between 98% and 90% (level 2); and systemic sO2 as measured by pulse oximetry was less than 90% (level 3). Following imaging, histological analysis of ocular tissue was conducted to evaluate for possible structural damage caused by the AR PAT imaging. AR PAT was able to resolve anatomical structures of the anterior segment of the eye, viewed through the cornea or anterior sclera. Histological studies revealed no ocular damage. On average, sO2 values (%) obtained with AR PAT were lower than sO2 values obtained with pulse oximetry (all p < 0.001): 86.28 ± 4.16 versus 99.25 ± 0.28, 84.09 ± 1.81 vs. 95.3 ± 2.6, and 64.49 ± 7.27 vs. 71.15 ± 10.21 for levels 1, 2 and 3 respectively. AR PAT imaging modality is capable of qualitative monitoring for deep tissue sO2 in rabbits. Further studies are needed to validate and modify the AR PAT modality specifically for use in human eyes. Having a safe, non-invasive method of in vivo imaging of sO2 in the anterior segment is important to studies evaluating the role of oxidative damage, hypoxia and ischemia in pathogenesis of ocular diseases.

[THE STRUCTURE OF LYMPHATIC CAPILLARIES OF THE CILIARY BODY OF THE HUMAN EYE].

Using light microscopy, immunohistochemistry and electron microscopy, the structural organization of interstitial spaces and vessels of the ciliary body of the human eye (n = 5) were studied. The ciliary body was found to contain wide interstitial spaces--tissue clefts bound by collagen fibers and fibroblasts. Organ-specific lymphatic capillaries were also demonstrated in the ciliary body. According to the present findings and the lymphatic region concept, the first 2 elements of the lymphatic region of the eye were described: tissue clefts--prelymphatics and lymphatic capillaries of the ciliary body. The third element of the lymphatic region are the lymph nodes of the head and neck.

Study of microcirculation of the ocular ciliary body in experimental kidney disease.

We studied disorders in ciliary body microcirculation in experimental chronic glomerulonephritis with tubulointerstitial nephritis and evaluated the hemodynamic effects of low-frequency pulsed electromagnetic field in this pathology. Laser Doppler flowmetry demonstrated vasospasm with reduced nutrient blood fl ow in the ciliary body of animals with experimental chronic glomerulonephritis with tubulointerstitial nephritis. The exposure to low-frequency pulsed electromagnetic field using developed technology will lead to significant reduction of the vascular tone and improve arterial blood supply to the microcirculatory bed.

Atrial natriuretic peptide and vasopressin-presence in the ciliary body of eye in the pig (sus domesticus).

The aqueous humor is produced in the ciliary body, therefore in this study we investigated the Atrial natriuretic peptide (ANP) and vasopressin (VP)-presence in the ciliary body of the pig eye since these peptide are involved in the homeostasis of body fluids. The results show ANP-presence in the epithelial cells and in the endothelial cells of the blood vessels and VP-presence in the epithelial cells, in the endothelium of canal of Schelmm and in the muscle cells of the blood vessels. These peptides might regulate the synthesis and the composition of the aqueous humor and regulate the hydrodynamic flow and haemodynamic flow of the blood.

Expression of the primary angle closure glaucoma (PACG) susceptibility gene PLEKHA7 in endothelial and epithelial cell junctions in the eye.

PURPOSE: The role of the recently identified primary angle closure glaucoma (PACG) susceptibility gene, pleckstrin homology domain containing, family A member 7 (PLEKHA7), in PACG is unknown. PLEKHA7 associates with apical junctional complexes (AJCs) and is thus implicated in paracellular fluid regulation. We aimed to determine PLEKHA7's localization in the eye and its association with AJCs to elucidate its potential role in PACG. METHODS: Total RNA from ocular tissues was isolated and analyzed by real-time PCR. Frozen and paraffin-embedded human globes were sectioned and used for immunohistochemistry and immunofluorescence analysis. RESULTS: Specific PLEKHA7 expression was found in the muscles, vascular endothelium, and epithelium of the iris, ciliary body and ciliary processes, trabecular meshwork (TM), and choroid. PLEKHA7 expression in musculature and vascular endothelium was confirmed with smooth muscle marker, SMA, and endothelium marker, PECAM-1, respectively. At the above sites, PLEKHA7 colocalization was seen with adherens junction markers (E-cadherin and ß-catenin) and tight junction markers (ZO-1). CONCLUSIONS: Specific localization of PLEKHA7 was found within PACG-related structures (iris, ciliary body, and choroid) and blood-aqueous barrier (BAB) structures (posterior iris epithelium, nonpigmented ciliary epithelium, iris and ciliary body microvasculature). The association of PLEKHA7 with AJCs in the eye suggests a potential role for PLEKHA7 in PACG via fluidic regulation. Novel expression of PLEKHA7 was also seen in the ocular smooth muscles and vascular endothelia.

The effect of vasopressin on ciliary blood flow and aqueous flow.

PURPOSE: Previous experiments have shown that arginine-vasopressin (AVP) reduces intraocular pressure (IOP) dose-dependently. The present study investigated the relationships between IOP, ciliary blood flow (CilBF), and aqueous flow (AqF) responses to AVP in anesthetized rabbits. METHODS: CilBF was measured by laser Doppler flowmetry and AqF by fluorophotometry. Mean arterial pressure (MAP) and IOP were monitored continuously and simultaneously. Perfusion pressure (PP) was varied mechanically. Four experimental protocols were performed: the dose-response (n = 11) and the pressure-flow relationship (n = 8) for CilBF and the effects on CilBF, and AqF at low (0.08 ng/kg/min; n = 14) and high AVP infusion rates (1.33 ng/kg/min; n = 12). RESULTS: AVP decreased CilBF and IOP dose-dependently. At the low AVP infusion rate, AqF was reduced by 21.48% ± 2.52% without changing CilBF significantly. The high AVP infusion rate caused a 24.49% ± 3.53% decrease of AqF and a significant reduction in CilBF (35.60% ± 3.58%). IOP was reduced by 9.56% ± 2.35% at low and by 41.02% ± 3.19% at high AVP infusion rates. Based on the Goldmann equation, the decrease of AqF at the low AVP infusion rate accounted for 77.1% of the IOP reduction, whereas at the high AVP infusion rate, decreased AqF accounted for 28.4% of the IOP decline. CONCLUSIONS: The results indicate that AVP can modulate IOP by different dose-dependent physiological mechanisms. The shifts of the CilBF-AqF relationship suggest that the reduction of AqF by the low AVP infusion rate is mainly provoked by inhibiting secretory processes in the ciliary epithelium. In contrast, at the high AVP infusion rate, the AqF reduction is caused by either reduced CilBF or more likely by a combined effect of reduced CilBF and secretory inhibition.

Sildenafil stimulates aqueous humor turnover in rabbits.

Sildenafil citrate increases ocular blood flow and accelerates the rate of anterior chamber refilling after paracentesis. The latter effect could have resulted from a reduction in outflow facility or from an increase in aqueous humor (AH) production. In this study, we used scanning ocular fluorophotometry to examine the effects of sildenafil on AH turnover, and thus, AH production in eyes of live normal rabbits. For this, the rate of aqueous humor flow (AHF) was quantified with a commercially available fluorophotometer that measured the rate of fluorescein clearance from the anterior segment, which predominantly occurs via the trabecular meshwork. After ≈2 h of control scans to determine the baseline rate of AHF, the rabbits were fed 33 mg of sildenafil and allowed ≈45 min for the drug to enter the systemic circulation. Thereafter, fluorescence scans were retaken for an additional 90-120 min. Sildenafil ingestion increased AHF by about 36%, from 2.31 µL/min to 3.14 µL/min (P < 0.001, as two-tailed paired data, n = 20 eyes). This observation indicates that sildenafil citrate, which is a phosphodiesterase type-5 inhibitor currently marketed as a vasodilator (e.g., Viagra, Revatio), stimulates AHF in rabbits. Our results seem consistent with reports indicating that the drug dilates intraocular arteries and augments intraocular vascular flow. These physiological responses to the agent apparently led to increased fluid entry into the anterior chamber. As such, the drug might have utility in patients with ocular hypotony resulting from insufficient AH formation.

[Ultrastructural features of vascular iridociliary system after biopuncture by antihomotoxic medicine].

OBJECTIVE: To reveal ultrastructural features of iridociliary vessels after biopuncture with antihomotoxic medicine. METHODS: Myopia model was created on 10 rabbits by injecting all trans-retinoic acid in catheter Vasofix Certo 24G in left internal carotid artery until we got low myopia. After six months of daily injections all rabbits had myopia from -2,0 to 3,0 D. Animals were separated into two groups: 5 rabbits with daily intradermal injection in three points of upper eye lid without medicine during 10 days and 5 rabbits with daily intradermal injection in three points of upper eye lid with Cerebrum Compositum N during 10 days. Morphology of iridociliary system was explored. RESULTS: Biopuncture in myopia model increases level of metabolic reactions in iridociliary system, supplies adaptive reserves by the hemodynamic enrichment of ciliary body vessels and balance of autonomic nervous system impulsation.

Dual effect of prostaglandins on isolated intraocular porcine ciliary arteries.

PURPOSE: Prostaglandin analogues are used to reduce the intraocular pressure (IOP) in glaucoma, but also affect the tone of the arteries supplying the ciliary body. Previously, the effect of prostaglandins has been studied on the extraocular ciliary arteries, whereas the effect on intraocular ciliary arteries has not been studied in detail. METHODS: Intraocular long posterior porcine ciliary arteries were isolated and mounted in a myograph system for isometric tension recording, and the effects of PGF2α , the prostaglandin analogue latanoprost, PGD2 , PGE2 , PGI2 and the thromboxane analogue U46619 were studied in the presence and absence of selective receptor antagonists. RESULTS: The prostaglandins PGD2 and PGE2 induced relaxation at low concentrations (10(-9) - 3 × 10(-7) m), which could be inhibited by blocking either the DP or the EP4 receptor, whereas PGD2 , PGE2 , PGF2α , latanoprost and U46619 induced contraction at high concentrations (10(-6) - 10(-5) m), which could be inhibited by blocking the TP receptor. Additionally, blocking of the FP receptor induced a right-shift of latanoprost-induced contraction. CONCLUSIONS: Prostaglandins with affinity to DP1 and EP4 receptors induce relaxation at low concentrations, and prostaglandins with affinity to TP and FP receptors induce contraction at high concentrations of intraocular porcine ciliary vessels in vitro. The findings may contribute to understanding the regulation of blood flow to the ciliary body.