Cyp2c44 epoxygenase-derived epoxyeicosatrienoic acids in vascular smooth muscle cells elicit vasoconstriction of the murine ophthalmic artery.

Cytochrome P450 (CYP) signalling pathway has been shown to play a vital role in the vasoreactivity of wild type mouse ophthalmic artery. In this study, we determined the expression, vascular responses and potential mechanisms of the CYP-derived arachidonic acid metabolites. The expression of murine CYP (Cyp2c44) and soluble epoxide hydrolase (sEH) in the wild type ophthalmic artery was determined with immunofluorescence, which showed predominant expression of Cyp2c44 in the vascular smooth muscle cells (VSMC), while sEH was found mainly in the endothelium of the wild type ophthalmic artery. Artery of Cyp2c44-/- and sEH-/- mice were used as negative controls. Targeted mass spectrometry-based lipidomics analysis of endogenous epoxide and diols of the wild type artery detected only 14, 15-EET. Vasorelaxant responses of isolated vessels in response to selective pharmacological blockers and agonist were analysed ex vivo. Direct antagonism of epoxyeicosatrienoic acids (EETs) with a selective inhibitor caused partial vasodilation, suggesting that EETs may behave as vasoconstrictors. Exogenous administration of synthetic EET regioisomers significantly constricted the vessels in a concentration-dependent manner, with the strongest responses elicited by 11, 12- and 14, 15-EETs. Our results provide the first experimental evidence that Cyp2c44-derived EETs in the VSMC mediate vasoconstriction of the ophthalmic artery.

Superselective Arterial Hyaluronidase Thrombolysis Is Not an Effective Treatment for Hyaluronic Acid-Induced Retinal Artery Occlusion: Study in a Rabbit Model.

BACKGROUND: Worldwide application of hyaluronic acid has brought about severe complications, including central retinal arterial occlusion, which leads to a deleterious effect on vision. The current study explored the efficacy of superselective arterial hyaluronidase thrombolysis in rabbit retinal artery occlusion induced by hyaluronic acid. METHODS: Occlusion of the internal/external ophthalmic artery in New Zealand White rabbits was induced with superselective injection of hyaluronic acid. Superselective subtraction angiography and fundus examination were conducted to confirm and evaluate the artery embolism. After 30 minutes of embolism, hyaluronidase was injected in the occluded artery through superselective arterial intubation. RESULTS: Compared with preoperative and contralateral eyes, the postoperative eyes showed the symptoms of central retinal arterial occlusion and embolization, confirmed by digital subtraction angiography. After intraarterial hyaluronidase thrombolysis, the embolization failed to dissolve as shown on funduscopic and angiographic examinations. CONCLUSIONS: Superselective ophthalmic artery intervention could accurately and successfully establish the animal models of retinal artery occlusion induced by hyaluronic acid. The precise occlusion site of the retinal artery and complete embolism were confirmed by ophthalmologic examinations. Intraarterial hyaluronidase thrombolysis might not be an effective method to treat retinal artery occlusion induced by hyaluronic acid.

Visual loss from dermal fillers.

BACKGROUND: An increasing number of people are undergoing non-surgical aesthetic procedures, especially injections of botulinum toxin and dermal fillers. While toxin injections have lower rates of complications, profound and serious consequences can arise with the use of dermal fillers. CASE: A 29-year-old woman presented to the eye casualty department with sudden visual loss, ptosis and ophthalmoplegia after having had non-surgical rhinoplasty in a beauty salon in West London. The filler was administered by a healthcare professional not registered with the General Medical Council (GMC) or similar governing body. DISCUSSION: Despite prompt measures on arrival at our service, the symptoms of visual loss, ptosis and ophthalmoplegia persisted. Attempts from the patient and medical services to report the incident (to trading standards and the police) were to no avail. CONCLUSION: This case highlights the poor treatment response to filler-related ophthalmic complications. It is also evident that in the United Kingdom, there appears to be poor regulation in the use of these products, a lack of clear guidelines for the management of their complications and finally no recourse for patients to challenge practitioners who lack medical registration and are not held accountable.

Angiographic investigation of orbital vascular variations in the rabbit and implications for endovascular intra-arterial chemotherapy models.

BACKGROUND: The New Zealand White rabbit (NZWR) is the first small-animal experimental model of intra-arterial chemotherapy (IAC) for retinoblastoma treatment. The NZWR has dual ophthalmic arteries (OA): the external OA (EOA) arises from the external carotid artery and the internal OA (IOA) from the internal carotid artery. We describe the technique that we have refined for OA catheterization in rabbits, and describe the angioanatomical variations in the OA supply to the NZWR eye and implications for IAC delivery, which were identified as part of a larger project exploring IAC effects in a rabbit retinoblastoma model. METHODS: We developed techniques to perform angiography of the external and internal carotid arteries and superselective angiography of the EOA and IOA in NZWR using transfemoral access and a microwire/microcatheter system. EOA and IOA supply to the eye was determined angiographically and recorded before selective OA catheterization and angiography. RESULTS: 114 rabbits underwent carotid angiographic evaluation and OA catheterization (161 total eyes evaluated, 112 right, 49 left). Most eyes had a single dominant arterial supply; either IOA or EOA. EOA was dominant in 73% (118/161), and IOA was dominant in 17% (27/161). Co-dominant supply was seen in 10% (16/161). Of the rabbits with bilateral OA catheterization, 25/47 (53%) had bilateral dominant EOA. CONCLUSION: Successful catheterization of the OA in the NZWR can be readily accomplished with nuanced technique. The external OA is the dominant arterial supply in the majority of NZWR eyes. These findings allow for successful reproduction of OA catheterization studies of IAC for retinoblastoma in NZWR.

Generation of Filler Emboli as a Mechanism for Filler-Related Blindness.

BACKGROUND: Intra-arterial injection of fillers can lead to occlusion of the ophthalmic artery or its branches supplying the retina or the optic nerve. The mechanism through which this occurs is incompletely understood. We investigated the possibility of generating microparticles after injecting commercially available fillers into a flowing system in vitro. METHODS: Three hyaluronic acid fillers and one calcium hydroxylapatite filler were injected into an artificial saline flow system mimicking arterial systolic blood pressure and corresponding to the diameter of the facial artery. All the saline at the end of the tube was collected, centrifuged, and inspected for filler particles. RESULTS: After injection into the system, all fillers immediately disintegrated into small particles that were carried downstream with the flow of the saline. The saline at the end of the tube contained collections of filler. CONCLUSION: Hyaluronic acid and hydroxylapatite fillers break up into small particles immediately after injection into a flowing system, generating emboli rather than a column of filler. The results of this study lead us to hypothesize another potential mechanism leading to filler-related blindness.

Incidence and predictors of ophthalmic artery occlusion in intra-arterial chemotherapy for retinoblastoma.

BACKGROUND: Retinoblastoma is the most common primary intraocular malignancy in children. OBJECTIVE: To determine the incidence of ophthalmic artery (OA) occlusion in patients treated with selective ophthalmic artery catheterization (OAC) for chemotherapy infusion for retinoblastoma. Also, to evaluate technical, anatomical, tumorous, and patient-related factors that are predictors of OA occlusion. METHODS: A retrospective chart review was performed for patients diagnosed with intraocular retinoblastoma and managed with intra-arterial chemotherapy (IAC). RESULTS: The total study cohort included 208 retinoblastoma tumors of 208 eyes in 197 consecutive patients who underwent 688 attempted IAC infusions overall with a total of 624 successful OAC infusions. The total incidence of ophthalmic artery thrombosis was 11.1% (23/208). The numbers of successful OAC procedures before diagnosing OA occlusion were one OAC in six cases (27.3%), two in seven cases (31.8%), three in four cases (18.2%), four in one case (4.5%), five in two cases (9.1%), and six in one case (4.5%). CONCLUSIONS: Local factors relating to the chemotherapy and selective microcatheterization of the OA are essential factors in the development of OA thrombosis, as seen by the association of OA thrombosis with the frequency of IAC.

Surgical outcomes of strabismus after iatrogenic ophthalmic artery occlusion caused by cosmetic filler injections.

BACKGROUND: To investigate the surgical outcomes of strabismus related to iatrogenic occlusion of the ophthalmic artery and its branches from cosmetic facial filler injection. METHODS: A retrospective study was performed on 6 patients who underwent strabismus surgery among 23 patients who had suffered occlusion of the ophthalmic artery and its branches after cosmetic facial filler injection. Initial, preoperative and final ocular motility examinations, the type of surgery and surgical outcomes were evaluated. RESULTS: At initial presentation, visual acuity was no light perception in 5 patients and hand motion in one patient. Five out of 6 patients showed initial ophthalmoplegia. Among these 5 patients, eye motility fully recovered in 3 patients although sensory strabismus developed during follow-up, while the remaining 2 patients had persistent ocular motility limitations. Strabismus surgery was performed at 2.2 ± 1.5 years after iatrogenic ophthalmic artery occlusion. Preoperatively, 5 of the 6 patients showed exotropia, and one patient had esotropia. Vertical deviation was found in 3 out of 6 patients in addition to the horizontal deviation. Successful outcome was achieved only in the 4 patients without persistent ophthalmoplegia after 1.4 ± 1.0 years from surgery. The other two patients with persistent ocular motility limitations failed to achieve successful alignment after surgery, and one patient eventually underwent evisceration due to phthisis bulbi. CONCLUSIONS: In our study, surgical outcomes of strabismus caused by cosmetic facial filler injection were successful only in patients without persistent ophthalmoplegia at the time of surgery.

Rabbit Model of Intra-Arterial Chemotherapy Toxicity Demonstrates Retinopathy and Vasculopathy Related to Drug and Dose, Not Procedure or Approach.

Purpose: To use our intra-arterial chemotherapy (IAC) rabbit model to assess the impact of IAC procedure, drug, dose, and choice of technique on ocular structure and function, to study the nature and etiology of IAC toxicity, and to compare to observations in patients. Methods: Rabbits received IAC melphalan (0.4-0.8 mg/kg), carboplatin (25-50 mg), or saline, either by direct ophthalmic artery cannulation, or with a technique emulating nonocclusion. Ocular structure/function were assessed with examination, electroretinography (ERG), fundus photography, fluorescein angiography, optical coherence tomography (OCT), and OCT angiography, prior to and 5 to 6 weeks after IAC. Blood counts were obtained weekly. We reviewed our last 50 IAC treatments in patients for evidence of ocular or systemic complications. Results: No toxicity was seen in the saline control group. With standard (0.4 mg/kg) melphalan, no vascular/microvascular abnormalities were seen with either technique. However, severe microvascular pruning and arteriolar occlusions were seen occasionally at 0.8 mg/kg doses. ERG reductions were dose-dependent. Histology showed melphalan dose-dependent degeneration in all retinal layers, restricted geographically to areas of greatest vascular density. Carboplatin caused massive edema of ocular/periocular structures. IAC patients experienced occasional periocular swelling/rash, and only rarely experienced retinopathy or vascular events/hemorrhage in eyes treated multiple times with triple (melphalan/carboplatin/topotecan) therapy. Transient neutropenia occurred after 46% of IAC procedures, generally after triple therapy. Conclusions: IAC toxicity appears to be related to the specific drug being used and is dose-dependent, rather than related to the IAC procedure itself or the specific technique selected. These rabbit findings are corroborated by our clinical findings in patients.

OPHTHALMIC VASCULAR EVENTS AFTER INTRA-ARTERIAL CHEMOTHERAPY FOR RETINOBLASTOMA: Real-World Comparison Between Primary and Secondary Treatments.

PURPOSE: To determine whether treatment order affects ophthalmic vascular event rates after intra-arterial chemotherapy (IAC) for retinoblastoma. METHODS: Patients who received IAC as primary or secondary treatment for retinoblastoma from January 2009 to January 2018 were included. All eyes were imaged with fundus photography and fluorescein angiography. Patient characteristics and vascular event rates were compared using t-test and Fisher's exact test. RESULTS: There were 196 patients treated with 682 infusions of IAC, divided into primary (no previous therapy, 98 eyes of 98 patients, 328 infusions) and secondary (after other therapy, 105 eyes of 98 patients, 354 infusions) treatment. Overall, ophthalmic vascular events were found after 5% of infusions (17% eyes). A comparison of ophthalmic vascular events (primary vs. secondary IAC), with mean three infusions per eye (median 3, range 1-7), revealed no difference in overall percentage of eyes affected (18% vs. 15%, P = 0.57). Adverse vascular events per eye included retinal vasculature attenuation (1% vs. 0%, P = 0.99), peripheral retinal pruning (1% vs. 0%, P = 0.99), branch retinal artery occlusion (0% vs. 1%, P = 0.99), central retinal artery occlusion (0% vs. 1%, P = 0.99), macular ischemia (0% vs. 2%, P = 0.51), vitreous hemorrhage (2% vs. 3%, P = 0.92), subretinal hemorrhage (1% vs. 0%, P = 0.99), retinal pigment epithelium atrophy (6% vs. 3% P = 0.43), choroidal atrophy (4% vs. 2%, P = 0.92), optic disk pallor (1% vs. 0%, P = 0.99), and ophthalmic artery occlusion (9% vs. 6%, P = 0.35). CONCLUSION: Ophthalmic vascular events after IAC for retinoblastoma affect only 5% of eyes per infusion (17% of treated eyes). Vascular event risk per eye is similar when using IAC as primary or secondary treatment.

Ocular and cerebral infarction from periocular filler injection.

A 20-year-old woman presented with loss of vision in her right eye and a "black nose" after receiving hyaluronic acid filler injections in her right glabella 1 month prior. Her vision was no light perception, and external examination revealed resolving skin necrosis at the nasal tip. A dilated fundus exam showed a fibrotic membrane emanating from a pale optic nerve and a diffusely atrophic retina with sclerotic vessels. An MRI demonstrated scattered right-sided parietal lobe infarcts. These findings were consistent with inadvertent cannulation of the supraorbital artery, followed by injection of filler into the internal carotid circulation. The product traveled in a retrograde fashion, occluding the right ophthalmic artery, right dorsal nasal artery, and arterial segments to the Circle of Willis. This case highlights the importance of understanding the complex vascular architecture of the periorbita and the mechanism by which such occlusions occur.

Current Treatment of Bilateral Retinoblastoma: The Impact of Intraarterial and Intravitreous Chemotherapy.

PURPOSE: To evaluate the management and outcomes of naïve bilateral retinoblastoma treated at a single-center over a 5-year period during the era of ophthalmic artery chemosurgery (OAC) and intravitreous chemotherapy. METHODS: Retrospective cohort study of 46 patients (92 eyes) with naïve bilateral retinoblastoma treated at Memorial Sloan Kettering Cancer Center between January 2012 and February 2017. Indirect ophthalmoscopy, fundus photography, ultrasonography, and ultrasonic biomicroscopy were used to evaluate clinical response. Patient, ocular, ocular progression-free, ocular recurrent event-free, and second ocular survivals were assessed by Kaplan-Meier estimates. Retinal toxicity was evaluated by electroretinography. Snellen visual acuity and complete blood count metrics were recorded. RESULTS: Sixty-four eyes (70%) in 41 patients (89%) received ophthalmic artery chemosurgery as part of their treatment. Twenty-six patients (56%) received tandem OAC (bilateral simultaneous infusions). Seven eyes were primarily enucleated. No eye receiving initial OAC was enucleated. There was a single secondary enucleation in an eye initially treated with focal therapy with anterior chamber recurrence. The 3-year Kaplan-Meier estimates for overall ocular, secondary ocular (survival after treatment for recurrence), progression-free, and recurrent event-free survival were 91.3% [95% confidence interval (CI) 83.4-95.5], 98.7% (95% CI 91.3-99.8), 91.5% (95% CI 83.0-95.8), and 78.9% (95% CI 68.2-86.3), respectively. Overall and secondary ocular survivals were 100% for International Classification of Retinoblastoma (ICRB) groups A-C. Overall ocular survival was 91.5% (95% CI 70-97.8) for ICRB group D and 71.4% (95% CI 47.1-79.4) for group E. Secondary ocular survival was 95.4% (95% CI 71.8-99.3) for ICRB group D and 100% for group E. There were no treatment-related deaths, three patients developed trilateral retinoblastoma (one died), and one patient (who did not receive OAC) developed metastatic disease and is in remission at 32-month follow-up. CONCLUSION: The majority (89%) of bilateral retinoblastoma patients in the current era and at this center were treated with OAC. This has resulted in saving a historic number of eyes. A quarter of eyes developed recurrent disease (defined as recurrent disease requiring any treatment including focal), the majority of which occurred in the first year after treatment, and all but one was saved. There has been no compromise in patient survival.

Growth patterns of survivors of retinoblastoma treated with ophthalmic artery chemosurgery.

Although studies from pediatric cancers (largely acute lymphoblastic leukemia) have shown that patients undergoing systemic chemotherapy may experience decreased growth velocity during the treatment phase, no such data exist for retinoblastoma patients treated with systemic chemotherapy or ophthalmic artery chemosurgery (OAC). The purpose of this study is to report growth patterns of our retinoblastoma (Rb) population who were treated with OAC in a retrospective, single center (Memorial Sloan Kettering Cancer Center) review of 341 patients treated between 2006 and 2016. Children who only received OAC were classified as naive; those who were treated initially with systemic chemotherapy and subsequently presented to our center for OAC were termed secondary; and a small group of patients who received single-agent systemic chemotherapy prior to OAC were labeled bridge. For all patients, height and weight were recorded at monthly intervals during OAC (short-term) and then annually during a follow-up period (long-term) up to 3 years after treatment. Excluded from this study were children who received external radiation therapy and those with genetic syndromes, which are independently associated with growth derangements. During OAC, there was no significant difference in growth velocity between the naïve and secondary groups. In either group, number of treatments also did not affect growth rate. Three years after the end of OAC, naïve patients were in the 68th percentile by height (95% CI 61.30, 74.63) compared to secondary patients in the 61st percentile (95% CI 51.1, 71.47). Both groups were in the same weight percentiles during the first two years of follow-up but at the three-year follow-up period, naïve patients were in the 63rd percentile (95% CI 57.4, 69.4) and secondary patients were in the 60th percentile (95% CI 50.4, 69.7). OAC for retinoblastoma does not appear to impact short-term growth velocity, weight gain during the treatment period or after three years.

Acute Effect of Hypervolemic Hemodilution on Retrobulbar Hemodynamics in Anterior Ischemic Optic Neuropathy.

PURPOSE: Ischemic ocular disorders may be treated by hypervolemic hemodilution. The presumed therapeutic benefit is based on a volume effect and improved rheological factors. The aim was to investigate the acute effect of intravenous hydroxyethyl starch on retrobulbar hemodynamics in patients with nonarteritic anterior ischemic optic neuropathy (NAION). METHODS: 24 patients with acute NAION were included. Retrobulbar hemodynamics were measured using color Doppler imaging before and 15 min after intravenous infusion of 250 cc 10% hydroxyethyl starch (HES). Peak systolic velocity (PSV), end diastolic velocity (EDV), and Pourcelot's resistive index (RI) were measured in the ophthalmic artery (OA), central retinal artery (CRA), and short posterior ciliary arteries (PCAs). RESULTS: After infusion of HES blood flow velocities significantly increased in the CRA (PSV from 7.53 ± 2.33 to 8.32 ± 2.51 (p < 0.001); EDV from 2.16 ± 0.56 to 2.34 ± 0.55 (p < 0.05)) and in the PCAs (PSV from 7.18 ± 1.62 to 7.56 ± 1.55 (p < 0.01); EDV from 2.48 ± 0.55 to 2.66 ± 0.6 cm/sec (p < 0.01)). The RI of all retrobulbar vessels remained unaffected. Blood pressure and heart rate remained unchanged. CONCLUSIONS: Hypervolemic hemodilution has an acute effect on blood flow velocities in the CRA and PCAs in NAION patients. Increased blood flow in the arteries supplying the optic nerve head may lead to a better perfusion in NAION patients. This trial is registered with DRKS00012603.

Pharmacokinetics, Tissue Localization, Toxicity, and Treatment Efficacy in the First Small Animal (Rabbit) Model of Intra-Arterial Chemotherapy for Retinoblastoma.

Purpose: Current intra-arterial chemotherapy (IAC) drug regimens for retinoblastoma have ocular and vascular toxicities. No small-animal model of IAC exists to test drug efficacy and toxicity in vivo for IAC drug discovery. The purpose of this study was to develop a small-animal model of IAC and to analyze the ocular tissue penetration, distribution, pharmacokinetics, and treatment efficacy. Methods: Following selective ophthalmic artery (OA) catheterization, melphalan (0.4 to 1.2 mg/kg) was injected. For pharmacokinetic studies, rabbits were euthanized at 0.5, 1, 2, 4, or 6 hours following intra-OA infusion. Drug levels were determined in vitreous, retina, and blood by liquid chromatography tandem mass spectrometry. To assess toxicity, angiograms, photography, fluorescein angiography, and histopathology were performed. For in situ tissue drug distribution, matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) was performed. The tumor model was created by combined subretinal/intravitreal injection of human WERI-Rb1 retinoblastoma cells; the tumor was treated in vivo with intra-arterial melphalan or saline; and induction of tumor death was measured by cleaved caspase-3 activity. Results: OA was selectively catheterized for 79 of 79 (100%) eyes in 47 of 47 (100%) rabbits, and melphalan was delivered successfully in 31 of 31 (100%) eyes, without evidence of vascular occlusion or retinal damage. For treated eyes, maximum concentration (Cmax) in the retina was 4.95 µM and area under the curve (AUC0→∞) was 5.26 µM·h. Treated eye vitreous Cmax was 2.24 µM and AUC0→∞ was 4.19 µM·h. Vitreous Cmax for the treated eye was >100-fold higher than for the untreated eye (P = 0.01), and AUC0→∞ was ∼50-fold higher (P = 0.01). Histology-directed MALDI-IMS revealed highest drug localization within the retina. Peripheral blood Cmax was 1.04 µM and AUC0→∞ was 2.07 µM·h. Combined subretinal/intravitreal injection of human retinoblastoma cells led to intra-retinal tumors and subretinal/vitreous seeds, which could be effectively killed in vivo with intra-arterial melphalan. Conclusions: This first small-animal model of IAC has excellent vitreous and retinal tissue drug penetration, achieving levels sufficient to kill human retinoblastoma cells, facilitating future IAC drug discovery.

Pharmacology of Serotonin Receptors Causing Contraction of Isolated Bovine Posterior Ciliary Arteries: Role in Ocular Blood Flow.

PURPOSE: To determine the serotonergic (5HT) receptor subtype mediating the contraction of bovine posterior ciliary arteries (BPCAs) in vitro. METHODS: Longitudinal isometric tension was measured in BPCA strips (4-5 mm) mounted in 25 mL organ baths containing oxygenated Krebs solution at 37°C. Cumulative contractile concentration-response (C-R) curves were generated for various 5-HT agonists to assess their potencies and maximal degrees of contraction. Multiple agonist C-R curves were also constructed in the presence and absence of receptor-selective antagonists to determine antagonist potencies using Schild plots. RESULTS: Selective and nonselective agonists for 5-HT receptors elicited concentration-dependent contractile responses in BPCAs with the following rank order of potency: MK-212 > BW723C86 > α-methyl-5-HT >5-methoxy-α-5-methyl-5-HT >> R-DO1 > >5-HT >> cabergoline >> 5-methoxy-dimethyl-tryptamine >> 2-methyl-5-HT >> tryptamine. Interestingly, both 8-OH-DPAT (5HT1A agonist) and quipazine (5HT3 agonist) did not elicit contractions in BPCAs. The contractions produced by BW723C86 (5-HT2B agonist) were antagonized by 5-HT receptor blockers, RS-127445 (5-HT2B antagonist), and M-100907 (5-HT2A antagonist), yielding antagonist pA2 values of 7.5 ± 0.12 (n = 4) and 6.2 ± 0.17 (n = 4), respectively. Furthermore, contractions elicited by MK-212 (5-HT2C agonist) was blocked by RS-102221 (5-HT2C antagonist), although noncompetitively. CONCLUSIONS: On the basis of the pharmacological profile of selective agonists and antagonists, we conclude that serotonin-induced contractions of the BPCA are mediated primarily by a combination of 5HT2C and/or 5HT2B receptors. It appears that 5-HT1A and 5-HT3 receptors are not involved in the contractile action of BPCAs to serotonin.

Embolization of palpebral and orbito-frontal fistulas: technical and anatomical considerations in treating high-flow superficial skin lesions with liquid embolics.

The treatment of palpebral and periorbital fistulas may be challenging due to the presence of multiple anastomosis with eloquent ophthalmic and intracranial vascular territories. Moreover, cosmetic and functional characteristics of this area pose unique challenges to open surgical approaches and endovascular therapy. We review the advantages and disadvantages of different liquid embolics in treating palpebral and periorbital fistulas as we describe three successfully treated cases. Moreover, we describe important anatomical landmarks that should be considered at the time of treatment of these lesions.

The Effect of Ophthalmic Artery Chemosurgery on Immune Function in Retinoblastoma Patients: A Single Institution Retrospective Analysis.

BACKGROUND: Ophthalmic artery chemosurgery (OAC) is associated with grade 3 and 4 neutropenia, however the effect on T-cell number and function is unknown. The purpose of this retrospective review was to confirm that patients treated with OAC do not develop immunosuppression warranting Pneumocystis pneumonia prophylaxis. PROCEDURE: IRB approval was obtained for a single center retrospective review of immune function tests in retinoblastoma patients who received OAC. RESULTS: Twenty-three patients received ≥3 cycles of OAC and had immune function testing (absolute CD4 count) performed at a median of 34 days postcompletion of therapy (range, 15 to 63 d). Only 1 patient had a low absolute CD4 count of 189 cells/µL (normal, 359 to 1570 cells/µL) 2 and a half months after IV carboplatin and 28 days after their third dose of OAC. This patient was found to have coexisting hypogammaglobulinemia. Repeat immune function testing normalized through continued OAC treatment. CONCLUSIONS: Clinically significant immune suppression appears rare following OAC alone, but patients previously treated with IV chemotherapy may be immunosuppressed and may benefit from pneumocystis pneumonia prophylaxis until the CD4 count recovers.