Persistent socket pain in a dog after the enucleation of the eye and its clinical management.

Persistent socket pain is a condition described in humans after enucleation of the eye. This report aims at describing this condition in dogs. A 10-year-old male-neutered crossbreed was presented to the referral veterinary surgeon for enucleation of the right ocular globe. Anaesthesia and surgery were uneventful although during the postoperative period the dog was reluctant to open the mouth and to be explored by the referral veteterinary surgeon. Despite treatment with meloxicam, paracetamol and tramadol, no improvements were observed. Ten weeks after surgery, the dog was referred to the Dick White referrals for further investigations. Ophthalmic examination was normal, though palpation of the wound triggered an avoidance response. Magnetic resonance imaging showed changes compatible with orbital cellulitis. The area of interest was evaluated with the use of the mechanical Von Frey filaments. A response, characterised by sudden turning of the head and attempts to withdraw it, was evoked with filament 4.93 (8.0 g) during stimulation of the periorbital area. After induction of anaesthesia, an ultrasound-guided injection containing levobupivacaine 0.5% and methylprednisolone was performed within the retrobulbar area. Three hours after recovery from anaesthesia, no discomfort was observed during palpation of the area. Re-evaluation was performed with the Von Frey filaments; no response could be evoked during testing with all 20 filaments (from 2.36 to 6.65) applied on either side of the face. The patient was discharged with a course of gabapentin and, 3 weeks after the intervention, the dog showed no clinical signs of pain. Persistent socket pain is an unpleasant sensation at the level of the enucleated orbit, and it should be regarded as a challenging condition to diagnose and treat. The MRI findings appeared to be essential to select the most appropriate interventional treatment. The injection of local anaesthetic and steroid into the retrobulbar space was useful for both confirming the diagnosis and treating pain by reducing the peripheral signalling and decreasing the residual inflammation.

Factors affecting eye conservation and metastasis in posterior uveal melanomas.

PURPOSE: To determine the effect of patient and tumor features and different treatments on eye removal (enucleation or exenteration) and metastasis in posterior uveal melanoma (PUM). METHODS: Retrospective analysis. Patient age (≤60 vs >60 years), sex (female vs male), visual acuity (VA, ≤20/40 vs >20/40), largest tumor basal diameter (LTBD), tumor thickness, tumor stage according to American Joint Committee on Cancer (AJCC) 8th edition, ciliary body involvement, distance to optic disc (OD)/fovea (≤3 mm vs >3 mm), OD involvement, and histopathology were evaluated. Primary treatment options were transpupillary thermotherapy, plaque radiotherapy, Cyberknife radiosurgery, exoresection, and eye removal. Risk factors for primary eye removal were determined using logistic regression test and those for secondary eye removal and metastasis with Cox regression analysis. RESULTS: Of 387 cases, 153 (39.5%) underwent primary eye removal. Multivariable risk factors for primary eye removal included AJCC tumor stage (p = 0.001, OR:4.586; p < 0.001, OR:34.545; p < 0.001, OR:103.468 for stages T2, T3, and T4 vs stage T1, respectively), and VA≤20/40 (p = 0.014, OR:2.597). Multivariable risk factors for secondary eye removal were VA≤20/40 (p = 0.019, RR:2.817) and AJCC stage T3 vs T1 (p = 0.021, RR:2.666). Eye preservation rates in patients undergoing eye-conserving treatments were 80.3%, 69.6%, and 51.5% at 5, 10, and 15 years, respectively. Metastasis-free survival rates were 81.0%, 73.0%, and 56.7% at 5, 10, and 15 years, respectively. Multivariable risk factors for metastasis included eye removal as primary treatment (p = 0.005, RR:2.828) and mixed type histopathology (p < 0.001, RR:4.804). DISCUSSION: Early diagnosis is crucial for both eye preservation and survival in PUM. Increasing AJCC tumor stage and lower VA were risk factors for eye removal in this study. Mixed type histopathology and primary eye removal were risk factors for metastasis.

Comparison of different laser-based enucleation techniques for benign prostate hyperplasia: A systematic review and meta-analysis.

BACKGROUND: To summarize the current evidence on different laser-based enucleation techniques for benign prostate hyperplasia and compare the efficacy and safety of en-bloc, two-lobe and three-lobe techniques. MATERIALS AND METHODS: Through a systematical search of multiple scientific databases in March 2021, we performed a systematic review and cumulative meta-analysis of the primary outcomes of interest according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and AMSTAR (Assessing the methodological quality of systematic reviews) Guidelines, whose protocol was registered with PROSPERO(CRD42021240684). RESULTS: A total of 9 studies were included. All three laser enucleation techniques had no statistically significant difference in terms of enucleated prostate weight, maximum urinary flow rate (Qmax), postvoid residual urine volume (PVR), international prostate symptom score (IPSS), transient UI (TUI), persistent UI (PUI) and early postoperative complications. A shorter enucleation time was associated with the en-bloc technique compared to three technique (MD: -8.26, 95%CI: -12.73--3.79, p = 0.0003), whereas no significant difference was found in en-bloc versus two-lobe technique (MD:0.97,95%CI: -0.30-2.24,p = 0.13) and two-lobe versus three-lobe technique (MD: -3.19, 95%CI: -7.45-1.06, p = 0.14). A higher enucleation rate was associated with the en-bloc and two-lobe technique (MD: 0.05, 95%CI: 0.00-0.10, p = 0.03; MD: 0.09, 95%CI: 0.01-0.17, p = 0.03, respectively). A superior QoL was related to the two-lobe enucleation technique compared to three-lobe technique (MD: 0.22, 95%CI: 0.06-0.39, p = 0.009), whereas no meaningful difference was found in the group of en-bloc versus two-lobe (MD: -0.12, 95%CI: -0.62-0.37, p = 0.62) and group of en-bloc versus three-lobe (MD: -0.14, 95%CI: -0.56-0.29, p = 0.52). CONCLUSIONS: En-bloc and two-lobe laser-based enucleation techniques are feasible and safe alternative to three-lobe technique with comparable surgical outcomes and similar functional outcomes. A superior enucleation efficiency was associated with En-bloc and the two-lobe techniques compared to the three-lobe technique.

Long-term outcomes after enucleation or plaque brachytherapy of choroidal melanomas touching the optic disc.

PURPOSE: To investigate local and systemic outcomes after enucleation, brachytherapy with ruthenium-106, iodine-125, notched and non-notched plaques and transpupillary thermotherapy (TTT) of choroidal melanomas touching the optic disc. METHODS AND MATERIALS: All patients treated for choroidal melanoma touching the optic disc at St. Erik Eye Hospital, Stockholm, Sweden between 1984 and 2015 (n = 165) were included. Retrospective clinicopathological data was collected and 3D dosimetry performed. RESULTS: Ninety-five patients (58 %) had been treated with ruthenium-106 brachytherapy, 21 (13 %) with iodine-125 brachytherapy and 49 (30 %) with enucleation. Median follow-up was 12.3 years. In simulations, some tumor areas were underdosed with non-notched plaques. Fifty of 116 patients (43 %) underwent a secondary brachytherapy (n = 5), enucleation (n = 29) or TTT (n = 16). In multivariate Cox Regressions, there were no significant differences in the risk for tumor progression or lack of regression between radioisotopes and notched and non-notched plaques. Adding TTT did not reduce the risk for a second treatment. The number of clock hours of circumpapillary tumor growth did not correlate to the risk for treatment failure or mortality. There were no significant differences in melanoma-related mortality for any treatment including enucleation. Kaplan-Meier disease-specific survival was 77 % at 5 years, 72 % at 10 years and 67 % at 20 years. CONCLUSION: Plaque brachytherapy of choroidal melanomas touching the optic disc entails a two to threefold increased risk for treatment failure. This risk is similar between radioisotopes, notched and non-notched plaque designs and if TTT is used or not. The high rate of treatment failure does not lead to increased mortality.

Streptococcus pneumoniae endophthalmitis: clinical settings, antibiotic susceptibility, and visual outcomes.

Streptococcus pneumoniae endophthalmitis is clinically more severe, more difficult to treat, and carry a higher risk of vision loss, evisceration, or enucleation. This study is to investigate the clinical settings, antibiotic susceptibility, and visual outcomes of S. pneumoniae endophthalmitis at a tertiary referral center in Taiwan. S. pneumoniae endophthalmitis was diagnosed in 38 eyes of 38 patients. The main clinical features were postcataract endophthalmitis (n = 13, 34%) and endophthalmitis associated with corneal ulcer (n = 12, 32%), trauma (n = 6, 16%), endogenous etiology (n = 4, 11%), trabeculectomy (n = 2, 5%), and pterygium excision-related scleral ulcer (n = 1, 3%). Presenting visual acuity ranged from counting fingers to no light perception. Pars plana vitrectomy with intravitreal antibiotics was performed in 17 eyes (39%) in primary or secondary treatments. S. pneumoniae isolates were susceptible to vancomycin (38/38, 100%), penicillin (37/38, 97%), ceftriaxone (37/38, 97%), cefuroxime (12/15, 80%), levofloxacin (13/15 ,87%), and moxifloxacin (15/17, 88%). Final visual acuity was better than 20/400 in 3 of 38 eyes (8%), 5/200 to hand motions in 3 eyes (8%), and light perception to no light perception in 32 eyes (84%). Ten eyes (26%) underwent evisceration or enucleation. Although S. pneumoniae isolates were susceptible to vancomycin, S. pneumoniae endophthalmitis had a very poor visual prognosis.

Small choroidal melanoma: outcomes following apical height dose brachytherapy.

AIM: To assess the outcomes of small choroidal melanoma following iodine-125 episcleral brachytherapy (apical height dose of 85 Gy). METHODS: Patients with small choroidal melanoma that underwent iodine-125 episcleral brachytherapy between January 2004 and December 2017 were reviewed. Inclusion criterion for this study was the COMS small tumour size (tumour apical height of 1.0-2.5 mm and largest basal diameter (LBD) <16.0 mm). Patients that received any form of prior therapy or adjuvant transpupillary thermotherapy were excluded. Outcome measures were visual acuity (VA), recurrence, ocular survival and metastasis at 3 years. Kaplan-Meier estimation was calculated for VA, recurrence, ocular survival and survival outcome (overall and metastasis-free survival rate) at 3 years. RESULTS: 161 cases of choroidal melanoma were included in this study, with the mean (SD) age of 59.6 (14.1) years, and 93 (58%) were males. The mean (SD) apical height for the tumours were 2.1 (0.4) mm and mean (SD) LBD was 8.3 (2.2) mm. The mean (SD, median) follow-up was 40.7 months (37.1, 25 months). The VA was 20/50 or better in 69%. Only one recurrence event (1%) and one enucleation event (1%) were observed. Overall survival was 97%, and no metastatic events were observed at 3 years. CONCLUSION: Small choroidal melanomas treated with iodine-125 episcleral brachytherapy have excellent outcomes. The majority (69%) of patients retained VA of 20/50 or better with very high local control and ocular survival rate (99.3%) with the absence of metastasis (100%).

Three-dimensional design of a geometric model for an ocular prosthesis in ex vivo anophthalmic socket models.

PURPOSE: Fitting a customized ocular prosthesis for anophthalmic patients entails an artisanal labour-exhausting process and is standardly based on impression moulding of the socket, which may be anatomically inaccurate. The objective of the study was to design an impression-free socket mould with three-dimensional (3D) technology. METHODS: The ex vivo anophthalmic socket models included one silicone, one fresh pig cadaver head and three fresh-frozen human cadaver heads. After intra-socket application with iodine substance, five observers obtained eighteen low-dose cone beam computed tomography (CBCT) scans and one observer one high-dose CBCT scan of each model. The observers designed non-impression 3D moulds of the socket with 3D software. For the human cadaver sockets 3D geometric models of the ocular prosthesis were rendered from the 3D mould of the socket and the mirrored cornea of the contralateral eye. RESULTS: The posterior surface of the 3D mould was highly accurate, with a mean absolute deviation of 0.28 mm, 0.53 mm, 0.37 mm and mean upper deviation of 0.53 mm, 0.86 mm, 1.17 mm, respectively, for the phantom, pig and human model. The intra- and interobserver repeatability and reproducibility of the 3D moulds and designs was good (<0.35 mm). The largest variation in the 3D geometric model was found at the junction of the 3D mould and mirrored cornea. CONCLUSION: 3D design of an impression-free geometric model for an ocular prosthesis with low-dose CBCT is highly accurate in ex vivo anophthalmic socket models. This novel method is a critical step towards the manufacturing of 3D printed ocular prostheses and requires validation in anophthalmic patients.

Unilateral retinoblastoma; natural history and an age-based protocol in 248 patients.

OBJECTIVES: We aimed to study the clinical state and prognosis of patients with unilateral retinoblastoma who were being treated at a paediatric comprehensive cancer centre in a limited-resource country, to assess the different phases of treatment and the success of different, more complex real-life models. SUBJECTS: In this retrospective study, we created a snapshot of our retinoblastoma database for the period between 2007 and 2015. Patients whose data were included in the study were followed up until 2016. Out of a total of 744 screened patients, we included data of 248 patients who had been diagnosed with unilateral retinoblastoma. RESULTS: As classified as per the International Retinoblastoma Classification, 1 patient presented with group A, 21 with group B, 39 with group C, 104 with group D and 83 with group E retinoblastoma. Chemotherapy was the initial line of treatment in 115 patients and enucleation in 133 others. Later, 141 patients (56.9%) required further management. Patients had a mean ocular survival time of 20.8 months. Nine patients developed extraocular disease at a later stage of management: five after upfront enucleation and four after neoadjuvant chemotherapy. Mean overall survival time stood at 90.2 months. Four and three deaths were recorded in groups D and E, respectively. A single patient died in the initial chemotherapy arm, while six passed away in the initial enucleation arm. CONCLUSION: Our study highlights the importance of initial chemotherapy and close follow-up after enucleation of classes D and E affected eyes even in absence of germline mutations.

Prospective phase II study of children affected by bilateral intraocular retinoblastoma with macular involvement of both eyes or in the only preserved eye. Macular tumor control, eye preservation rate, and visual outcome.

BACKGROUND: Conservative treatments of intraocular retinoblastoma often consist of chemotherapy and focal treatments. The protocols vary and currently may combine two or three drugs, with different number of cycles, associated to the ocular treatments. In case of macular/paramacular involvement, tumor location and retinal scars induced by focal treatments often have a major negative impact on final visual outcome. METHODS: This study aimed to include children affected by bilateral intraocular macular/paramacular retinoblastoma in a prospective phase II study. The protocol consisted of six cycles of a three-drug combination (vincristine, etoposide, carboplatin), and the addition of macula-sparing transpupillary thermotherapy (TTT) to the third cycle. The primary endpoint was the local control rate without external beam radiotherapy (EBR) and/or enucleation. RESULTS: Nineteen patients (26 eyes) were included from July 2004 to November 2009. Thirteen eyes belonged to group V of the Reese-Ellsworth classification and 10 to group D of the International Intraocular Retinoblastoma Classification. Macular/paramacular tumors were treated with chemotherapy alone in nine eyes, and with chemotherapy associated with macula-sparing TTT in 17 eyes. Four eyes experienced macular relapse. At a median follow up of 77 months, 23 eyes (88.5%) were saved without EBR, two were enucleated and one received EBR. The median visual acuity of the 24 saved eyes was 20/50. No severe adverse effect was observed. CONCLUSION: Six cycles of a three-drug combination associated with macula-sparing TTT achieved good tumor control, improved eye preservation rates without EBR, and decreased macular damage, often providing satisfactory visual results with long-term follow up.

Modern treatment of retinoblastoma: A 2020 review.

Retinoblastoma management remains complex, requiring individualized treatment based on International Classification of Retinoblastoma (ICRB) staging, germline mutation status, family psychosocial factors and cultural beliefs, and available institutional resources. For this 2020 retinoblastoma review, PubMed was searched for articles dated as early as 1931, with an emphasis on articles from 1990 to the present day, using keywords of retinoblastoma, chemotherapy, intravenous chemotherapy, chemoreduction, intra-arterial chemotherapy, ophthalmic artery chemosurgery, intravitreal chemotherapy, intracameral chemotherapy, cryotherapy, transpupillary thermotherapy, laser, radiation, external beam radiotherapy, plaque radiotherapy, brachytherapy, and enucleation. We discuss current treatment modalities as used in the year 2020, including intravenous chemotherapy (IVC), intra-arterial chemotherapy (IAC), intravitreal chemotherapy (IvitC), intracameral chemotherapy (IcamC), consolidation therapies (cryotherapy and transpupillary thermotherapy [TTT]), radiation-based therapies (external beam radiotherapy [EBRT] and plaque radiotherapy), and enucleation. Additionally, we present a consensus treatment algorithm based on the agreement of three North American retinoblastoma treatment centers, and encourage further collaboration amongst the world's most expert retinoblastoma treatment centers in order to develop consensus management plans and continue advancement in the identification and treatment of this childhood cancer.

Iontophoresis-Assisted Rose Bengal and Green Light Corneal Cross-Linking.

PURPOSE: To evaluate the effects of the application of iontophoresis-assisted rose bengal and green light cross-linking (I-RGX) therapy on enucleated rabbit eyes for corneal biomechanical parameters, dye diffusion rates, and green light levels reaching deep tissues and to compare these parameters with a standard rose bengal and green light cross-linking (RGX) therapy. METHOD: Forty-five enucleated rabbit eyes were used in this study. To evaluate biomechanical changes, corneas were divided into the following 4 groups: the control group, the 0.1% rose bengal application group, the RGX group (100 J/cm), and the I-RGX group (100 J/cm). After this, corneal strips were evaluated with a uniaxial extensometer. To assess corneal dye diffusion, postprocedure dye depth was recorded with anterior segment optic coherence tomography. The amount of irradiation passing through the cornea during irradiation with 250 mW/cm irradiation power was measured with a laser power meter at the first, third, and seventh minutes. RESULTS: In the I-RGX-treated group especially, the mean elastic modulus and corneal stiffness values were about 4.7 times higher when compared with the controls and about 2.2 times higher than those in the RGX group. The rose bengal diffusion depth was 26.63% ± 3.84% of the total corneal thickness in the rose bengal drop group, but this value increased to 42.22% ± 4.77% in the iontophoresis group (<0.001). After iontophoresis, an average of 98% of the 100 J/cm green light was kept in the cornea. CONCLUSIONS: I-RGX is a very useful method for increasing corneal biomechanical strength and is highly effective in increasing the amount of corneal dye diffusion into the cornea while also minimalizing the amount of laser passage reaching deeper tissues.

A 20-year audit of retinoblastoma treatment outcomes.

OBJECTIVES: To evaluate the long-term treatment outcomes in intraocular retinoblastoma (RB) including the associated factors for eventual treatment with external beam radiotherapy (EBRT) and enucleation as well as to analyse the risk factors for metastasis and death in extraocular RB. METHODS: Retrospective analysis of 390 eyes from 256 (89.8%) intraocular RB and 29 (10.2%) extraocular RB cases diagnosed and treated between October 1998 and May 2018 at one of the largest tertiary care centers in Turkey. RESULTS: Of 351 intraocular RB eyes, 53.3% had group D/E disease at presentation. 75 (21.4%) of 351 eyes underwent primary enucleation. Of the remaining 276 eyes undergoing eye-conserving treatments, 201 (72.8%) were salvaged. Most of these eyes were treated using intravenous chemotherapy and/or focal treatments [transpupillary thermotherapy (TTT) and cryotherapy] initially. EBRT was eventually required in 48 (17.4%) eyes and secondary enucleation in 75 (27.2%) eyes. At mean follow-ups of 76.7 and 39.7 months for intraocular and extraocular RB cohorts, respectively, 180 (46.2%) eyes underwent primary/secondary enucleation and exenteration. Overall, 13 cases developed metastasis and 9 died. Two patients with trilateral RB also expired. Multivariable risk factors for enucleation were the presence of vitreous seeds (p < 0.001), absence of EBRT administration (p = 0.033), 5-9 TTT applications compared with no TTT (p = 0.031), and each 1 mm increase in tumour base diameter (p < 0.001). Univariate factors predictive of metastasis were the presence of extraocular RB detected by imaging methods (p < 0.001) and extrascleral/optic nerve cut end involvement at histopathological examination (p < 0.001). CONCLUSIONS: In our series, 72.8% of the intraocular RB eyes undergoing eye-conserving treatments were saved. The globe salvage rate for all intraocular and extraocular RB eyes was 53.8% and the overall survival rate was 96.1%.

Validation of a Comprehensive Clinical Algorithm for the Assessment and Treatment of Microbial Keratitis.

PURPOSE: To validate a comprehensive clinical algorithm for the assessment and treatment of microbial keratitis (MK). DESIGN: Retrospective cohort study. METHODS: The "1, 2, 3 Rule" for the initial management of MK was conceived by Vital and associates in 2007 to inform the decision as to when to perform corneal cultures. The rule is invoked when any 1 of 3 clinical parameters is met: ≥1+ anterior chamber cells, ≥2 mm infiltrate, or infiltrate ≤3 mm distance from the corneal center. When the rule is met, we added the mandatory use of fortified topical antibiotics after cultures are obtained. We compared outcomes of cases presenting to Massachusetts Eye and Ear 2 years before (Group I, n = 665) and after (Group II, n = 767) algorithm implementation. The primary composite outcome was a vision-threatening complication, such as corneal perforation. RESULTS: At a median follow-up of 67.0 and 60.0 days, respectively, 172 patients experienced a vision-threatening complication (Group I, 12.9% vs Group II, 11.2%, P = .51). While the algorithm codified conventional management practice at either end of disease severity, the effect of algorithm-augmented care was best appreciated in patients with lesions satisfying only 1 criterion. In this group, there was an increase in the proportion of patients undergoing culture at presentation (54.6% vs 67.7%, P = .006), fortified antibiotic prescription (29.7% vs 53.9%, P < .001), and reduction in vision-threatening complications (9.7% vs 1.8%, P = .001). The proportion of patients who were not cultured at presentation but later required culturing decreased (13.4% vs 5.1%, P = .001), as did patients who did not meet any criteria but were nonetheless cultured (23.9% vs 8.5%, P < .001). Multiple logistic regression showed that all algorithm parameters were independently associated with outcome: ≥1+ anterior chamber cells (odds ratio [OR] 1.66, 95% confidence interval 1.09-2.52); ≥2 mm infiltrate (OR 4.74, 2.68-8.40); and ≤3 mm from corneal center (OR 2.82, 1.85-4.31), confirmed with comparison to a bootstrapped sample (n = 10,000). CONCLUSIONS: The implementation of this algorithm reduced vision-threatening complications for patients with lesions satisfying only 1 criterion, arguably the most difficult patients in whom to judge disease severity. Implementation also led to a decrease in patients receiving unnecessary care.

A matched-pair analysis of patients with medium-sized prostates (50 cc) treated for male LUTS with HoLEP or TURP.

OBJECTIVES: To evaluate perioperative parameters, early functional outcomes, and the safety profile in a matched-pair analysis of lower urinary tract symptom (LUTS) patients treated with holmium laser enucleation of the prostate (HoLEP) or transurethral resection of the prostate (TURP). METHODS: We conducted a retrospective, matched-pair analysis of 2011 men treated for LUTS in our institution from 2013 to 2017. In the final analysis, 197 patients (HoLEP n = 97; TURP n = 98) were matched for prostate size (50 cc), age, and body mass index, and both cohorts were compared for demographic parameters, clinical outcomes, and adverse events according to the Clavien-Dindo classification. RESULTS: The perioperative assessment revealed a significantly higher tissue retrieval percentage of 75.4% (interquartile range [IQR] 64-81.2) after HoLEP in comparison to 47.3% (IQR 40-54.7) after TURP (P <.001). A shorter surgery time was reported for TURP with a median time of 55.5 minutes (IQR 48-70.5), whereas the median time for HoLEP was 62 minutes (IQR 51-85) (P =.006). The median improvements in International Prostate Symptom Score (IPSS) were 11 points (IQR 5.5-17) and 7 points (IQR 3-14) for HoLEP and TURP, respectively (P =.007). Peak urinary flow rate (Qmax ) increased more after HoLEP (12.0 mL/s; IQR 7-23) than after TURP (8.5 mL/s; IQR 5-18.25) (P =.028). With an overall incidence of adverse events of 6% (n = 6) compared to 16% (n = 16%), significantly fewer complications occurred after HoLEP than after treatment with TURP (P <.05). CONCLUSIONS: HoLEP is not only an attractive alternative for the enucleation of larger prostates, but it must be considered a size-independent technique with the potential to outdo the current reference method TURP.

Outcomes of neonatal retinoblastoma in pre-chemotherapy and chemotherapy eras.

Purpose: To quantify outcomes for neonatal retinoblastoma patients treated during the pre-chemotherapy (1980-1994) and chemotherapy (1995-2018) eras. Methods: Retrospective review of retinoblastoma patients diagnosed within the first 28 days of life between 1/1/1980 and 11/30/2018. Student's t-test, Chi-square, and Fisher's exact test were performed to compare treatments and outcomes by era. Results: There were 68 patients with neonatal retinoblastoma (12% unilateral and 88% bilateral). According to era (pre-chemotherapy vs. chemotherapy), the number of treated patients was 26 (38%) vs. 42 (62%). Primary treatment was external beam radiotherapy (50% vs. 1%,P < 0.001), plaque radiotherapy (17% vs. 0%,P < 0.001), focal treatment (transpupillary thermotherapy or cryotherapy) only (21% vs. 14%,P= 0.33), intravenous chemotherapy (0% vs. 81%,P < 0.001), enucleation (10% vs. 4%,P= 0.26), or exenteration (2% vs. 0%,P= 0.37). Outcomes included tumor control (79% vs. 94%,P= 0.02), globe salvage (75% vs. 91%,P= 0.02), final gross visual acuity for salvaged eyes 20/200 or better (66% vs. 89%,P < 0.01), and death (19% vs. 0%,P < 0.01). Conclusion: Chemotherapy advancements for neonatal retinoblastoma have improved tumor control, globe salvage, visual acuity, and patient survival.

Comparison between patient-reported outcomes after enucleation and proton beam radiotherapy for uveal melanomas: a 2-year cohort study.

BACKGROUND: Uveal melanomas affect 2-8 per million Europeans each year. Approximately 35%, are treated by enucleation. Proton beam radiotherapy (PBR) can be an eye-conserving alternative to enucleation for patients who wish to retain the eye. Both treatments have adverse effects, and it is difficult for clinicians and patients to make fully informed choices between them because the relative effects of enucleation and PBR on patient-reported outcomes are unknown. METHODS: We compared differential effects of enucleation and PBR on patient-reported outcomes on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Ophthalmological module (EORTC QLQ- OPT30) in a consecutive sample of 115 treated patients ~ 6, 12 and 24 months after diagnosis. Pre-treatment demographic variables, unrelated health problems, vision in the fellow eye, tumour characteristics and prognosis for metastatic disease were statistically controlled. RESULTS: Patients treated by enucleation experienced greater functional problems at 6 months, which abated at 12 and 24 months (P = 0.020). PBR patients reported greater impairments of central and peripheral vision (P = 0.009) and reading difficulties (P = 0.002) over 24 months. Treatment modality did not influence difficulty in driving (P = 0.694), ocular irritation (P = 0.281), headaches (P = 0.640), appearance concerns (P = 0.187) or worry about recurrence (P = 0.899). CONCLUSIONS: When making treatment decisions, it is important that patients and clinicians consider long-standing difficulties of visual impairment associated with PBR and temporary 6-month difficulties in activities related to depth perception associated with enucleation.

Metastases and death rates after primary enucleation of unilateral retinoblastoma in the USA 2007-2017.

BACKGROUND/AIMS: Enucleation for retinoblastoma is performed less often in the past decade due to increasingly widespread alternative therapies, but enucleation remains an important option. There is a paucity of reports on the current incidence of metastases and metastatic deaths in unilateral retinoblastoma from US centres. METHODS: Retrospective chart review at five tertiary retinoblastoma centres in the USA for unilateral retinoblastoma patients treated with primary enucleation, 2007-2017, with >1 year of follow-up or treatment failure. RESULTS: Among 228 patients (228 eyes), there were nine metastases (3.9%) and four deaths (1.7%). The Kaplan-Meier estimate at 5 years for metastasis-free survival was 96% (95% CI, 94% to 99 %), and for overall survival was 98% (95% CI 96% to 100%). All metastases were evident within 12 months. Histopathology revealed higher risk pathology (postlaminar optic nerve and/or massive choroidal invasion) in 62 of 228 eyes (27%). Of these higher risk eyes, 39 received adjuvant chemotherapy. There were four subsequent metastases in this higher risk pathology with adjuvant chemotherapy group, with three deaths. Of the nine overall with metastases, seven (78%) showed higher risk pathology. All metastatic patients were classified as Reese-Ellsworth V and International Classification of Retinoblastoma Groups D or E. Initial metastases presented as orbital invasion in seven of nine cases. CONCLUSIONS: Primary enucleation for unilateral retinoblastoma results in a low rate of metastatic death, but is still associated with a 3.9% chance of metastases within a year of enucleation. Most but not all patients who developed metastases had higher risk histopathological findings.

Retinoblastoma: hacia un diagnóstico más precoz / Retinoblastoma: towards an earlier diagnosis

OBJETIVOS: El número de enucleaciones y secuelas visuales por retinoblastoma es elevado. El objetivo del estudio fue evaluar diferentes aspectos diagnósticos y plantear estrategias que ayuden a mejorar el manejo clínico del retinoblastoma. Método: Estudio retrospectivo de 38 pacientes con retinoblastoma estudiados genéticamente (29 unilaterales, 9 bilaterales). Se evaluaron la edad de inicio, los signos clínicos y el tiempo de evolución, el número de enucleaciones, el momento de realización y la supervivencia a 5 años. Resultados: La leucocoria fue el signo clínico fundamental (presente en el 90% de los casos). El retraso diagnóstico medio fue de 3,2 meses. Entre los casos unilaterales se enuclearon el 76% de los ojos y en las formas bilaterales el 55%. Solo se encontró un fallecimiento entre los 25 pacientes seguidos durante al menos 5 años. Conclusiones: Las estrategias de diagnóstico y tratamiento del retinoblastoma necesitan ser actualizadas. Para ello, una buena coordinación entre pediatras y oftalmólogos es esencial. El manejo en centros de referencia, que dispongan de la tecnología y experiencia necesarias, debería contribuir a aumentar la tasa de preservación de órganos

OBJETIVOS: The number of enucleations and visual sequels due to retinoblastoma is high. The aim of this study was to evaluate the different diagnostic aspects and propose strategies that might improve the clinical management of this condition. Method: A retrospective study was conducted on 38 patients with retinoblastoma studied genetically (29 unilateral, 9 bilateral). The evaluation included: age of onset, clinical signs, and time since onset, number of enucleations, time to diagnosis, and survival at 5 years. Results: Leukocoria was the main clinical sign (present in 90% of cases). The mean diagnostic delay was 3.2 months. Among the unilateral cases, the eyes were enucleated in 76%, and 55% in the bilateral forms. Only one death was found among the 25 patients followed-up for at least 5 years. Conclusions: Retinoblastoma diagnostic and treatment strategies need to be updated. Good coordination between paediatricians and ophthalmologists is essential for this. Its management in reference centres, which have the necessary technology and experience, should contribute to increase the rate of organ preservation

[ADVANCES IN THE TREATMENT OF RETINOBLASTOMA AT HADASSAH IN THE LAST THREE DECADES].

INTRODUCTION: Retinoblastoma (RB) is a malignant tumor presenting in the eyes of infants and children, which endangers life, the eye and vision. The treatment of RB has undergone marked changes in recent years, and great progress has been made in our ability to preserve eyes. Over the last three decades most Israeli patients with RB have been treated in the National Specialty Ocular Oncology Service at the Hadassah-Hebrew University Medical Center in Jerusalem. AIMS: To describe advances in the primary treatment of RB with an emphasis on eye-preserving treatments. METHODS: The study included a retrospective cohort of patients who were diagnosed and treated at our center over the last three decades. Review of patients' records was approved by the Hadassah IRB. RESULTS: From 1988 to 2014 we diagnosed 290 children (138 girls - 47.6%). The mean age at diagnosis (±SE) was 18.1±1.2 months, median 12.5 months. RB was unilateral in 55.6% of the cases, bilateral in 41.3% and unilateral multifocal in 3.1%. There was an even distribution of disease severity (IRB grouping). Since the advent of IV chemotherapy (IVC) there has been a decrease in the rate of eye enucleation from ~90% to ~30% of the children until the year 2000 with a stable rate thereafter. In the years 1990-2000 there was an increase followed by a decrease in the use of primary external beam radiotherapy (EBRT), and a parallel small increase in the use of brachytherapy from the mid '90s until today. The recently introduced novel treatments - intravitreal (IVitC) and intra-arterial chemotherapy (IAC) - were used as a complimentary treatment to IVC, and not yet as a single primary modality until 2014. CONCLUSIONS: IVC replaced the need to enucleate in most of the cases, but 30% of children still require a primary enucleation. DISCUSSION: IVC usually requires additive treatments (thermal-cryotherapy, trans-pupillary thermotherapy - TTT, brachytherapy and/or local chemotherapy - IVitC and IAC) and with the use of multi-modal therapy many eyes can be preserved. In the period reported in the current manuscript, the use of IAC as a primary treatment approach was only used in isolated cases. In Summary, There have been significant advances in our ability to save eyes, and the field continues to progress.