Severe Visual Acuity Decrease Research Articles

Visual dysfunction and neurodegeneration caused by severe inflammatory optic neuropathy after coil embolization of a paraclinoid aneurysm: illustrative case.

Visual impairment due to delayed optic neuropathy is a rare complication of the endovascular treatment of paraclinoid aneurysms. An inflammatory response induced in the treated aneurysm wall is a known mechanism underlying this pathophysiology. The authors describe a case with severe and progressive optic neuropathy leading to neuronal degeneration and severe visual dysfunction. A 42-year-old female with a history of surgical clipping for a paraclinoid aneurysm presented with a recurrence. Although the patient was unaware of any visual dysfunction, a preoperative ophthalmological examination revealed mild inferior quadrantanopia in the left eye. The coil embolization procedure was uneventful; however, the following day, the patient experienced progressive visual impairment, which worsened despite the initiation of steroid therapy. Ophthalmological examination revealed a severe decrease in visual acuity and further deterioration of the visual field. Magnetic resonance imaging showed remarkable swelling and edema of the left optic nerve adjacent to the treated aneurysm. Despite continued steroid therapy, the patient's visual function did not recover well due to subsequent optic nerve degeneration. Optic neuropathy after endovascular procedures can lead to severe visual dysfunction. Careful management is essential, particularly when treating a symptomatic paraclinoid aneurysm, even if symptoms are only apparent on detailed examination.

The dose-response relationship of subretinal gene therapy with rAAV2tYF-CB-hRS1 in a mouse model of X-linked retinoschisis.

X-linked retinoschisis (XLRS), due to loss-of-function mutations in the retinoschisin (RS1) gene, is characterized by a modest to severe decrease in visual acuity. Clinical trials for XLRS utilizing intravitreal (IVT) gene therapy showed ocular inflammation. We conducted a subretinal dose-response preclinical study using rAAV2tYF-CB-hRS1 utilizing the Rs1 knockout (Rs1-KO) mouse to investigate short- and long-term retinal rescue after subretinal gene delivery. Rs1-KO mice were subretinally injected with 2 μL of rAAV2tYF-CB-hRS1 vector with 8E9 viral genomes (vg)/eye, 8E8 vg/eye, 8E7 vg/eye, or sham injection, and compared to untreated eyes. Reconstitution of human RS1 protein was detected using western blotting. Analysis of retinal function by electroretinography (ERG) and structural analysis by optical coherence tomography (OCT) were performed at 1, 2, 3, 5, 7, and 12 months post injection (MPI). Immunohistochemistry (IHC) was performed to evaluate cone rescue on the cellular level. Functional vision was evaluated using a visually guided swim assay (VGSA). Western blotting analysis showed human RS1 protein expression in a dose-dependent manner. Quantification of western blotting showed that the RS1 protein expression in mice treated with the 8E8 vg dose was near the wild-type (WT) expression levels. ERG demonstrated dose-dependent effects: At 1 MPI the 8E8 vg dose treated eyes had higher light-adapted (LA) ERG amplitudes in 3.0 flash and 5 Hz flicker compared to untreated (p < 0.0001) and sham-treated eyes (p < 0.0001) which persisted until the 12 MPI endpoint, consistent with improved cone function. ERG b-wave amplitudes were higher in response to dark-adapted (DA) 0.01 dim flash and 3.0 standard combined response (SCR) compared to sham-treated (p < 0.01) and untreated eyes (p < 0.001) which persisted until 3 MPI, suggesting short-term improvement of the rod photoreceptors. All injections, including sham-treated, resulted in a cyst severity score of 1 (no cavities), with significant reductions compared to untreated eyes up to 3 MPI (p < 0.05). The high and low dose groups showed inconsistent ERG improvements, despite reduced cyst severity, emphasizing the dose-dependent nature of gene augmentation's efficacy and the tenuous connection between cyst reduction and ERG improvement. IHC data showed a significant cone rescue in eyes treated with the 8E8 vg dose compared to sham-treated and untreated eyes. VGSA showed better functional vision in 8E8 vg dose treated mice. Eyes treated with the highest dose showed occasional localized degeneration in the outer nuclear layer. Our data suggest that a dose of 8E8 vg/eye subretinally improves retinal function and structure in the Rs1-KO mouse. It improves cone function, rod function, and reduces cyst severity. Sham treatment resolves schisis cysts, but 8E8 vg/eye is needed for optimal retinal electrical function rescue. These findings offer a promising path for clinical translation to human trials.

PREVALENCE OF DECREASED VISUAL ACUITY IN ELEMENTARY SCHOOL-AGE CHILDREN PATIENTS AT KUTIME HEALTH CENTER, TOLIKARA DISTRICT, PAPUA PEGUNUNGAN PROVINCE

Introduction: Vision has an important role in a child's learning process, and has a correlation with a child's achievement at school. The aim of this study was to determine the prevalence of decreased visual acuity or refractive errors in primary school-age children in the working area of the Kutime Health Center, Nabunage District, Tolikara Regency.&#x0D; Methods: This research is descriptive in nature with a cross-sectional research design and a total sampling technique. The sample for this study were all pediatric patients aged 6-12 years who went to the Kutime Health Center during the period June 2022 to December 2022. Examination of visual acuity in this study used the Snellen Chart.&#x0D; Results: Participants totaled 105 children with prevalence of decreased visual acuity at the Kutime Health Center at 5.71%. The prevalence is higher in girls (6.81%) than boys (4.91%). Based on the affected eyes, the left eye (5.71%) obtained refractive error more than the right eye (3.8%). Decreased vision found in this study was 6/15, 6/12, 6/10, and 6/7.5 which means it is included only in the category of mild vision loss. There were no children (0%) who experienced a moderate and severe decrease in visual acuity in the right or left eye. There were no children (0%) who experienced a profound reduction, reduced visual acuity to near blindness, and blindness without light perception in the right or left eye. The most common age range for children is in the age range of 10-12 years (7.89%). Most of the children with decreased visual acuity came from the village of Kabelogok (12.5%).&#x0D; Conclusion: The prevalence rate of eye disorders in the Kutime Health Center, Nabunage District, Tolikara Regency is 5.71%, this figure is still above the Papua Province rate, which is 2.4% and nationally, which is 4.6%. Advice that can be given to parents and the school is to carry out routine screening in order to be able to detect decreased visual acuity in children's eyes early so that they can be intervened more quickly so as not to exacerbate children's decreased visual acuity in the future.

66 Optic neuritis in children

IntroductionOptic neuritis (ON) are rare in children. They are due to inflammation of the optic nerve which results in a sudden drop in visual acuity, or amputation of the visual field. They are often secondary to an infectious disease or vaccination, but they can be part of auto-inflammatory, demyelinating or systemic diseases. The features of optic neuritis in children are different from adults as regards high rate of bilateral involvement, poor visual acuity, and papillitis.AimOur aim is to describe the clinical and therapeutic outcomes of patients diagnosed with optic neuritis in the general pediatrics department at the CHU of Bab el Oued in Algiers.MethodsIt is a retrospective, descriptive study of patients who were treated for optic neuritis in our hospital over a period of three years (January 2018 to April 2021).ResultsThere were 7 cases, 4 girls and 3 boys with F: M of 1.3:1, mean age of 10 years and age range of 6–13 years. The first manifestation was a decrease in visual acuity in all cases, 12 eyes affected, with bilateral involvement in 5 patients. Visual acuity decrease was severe < 3/10 in 80% of cases. The visual field was pathological in 2 cases (narrow, central scotoma). All patients had headaches.Retrobulbar involvement was confirmed by visual evoked potentials in all patients, they showed demyelinating involvement. Three patients presented papillitis.The diagnostic work-up included cerebral imaging which showed old nodular abnormalities of signal of the subcortical white matter in one patient.CSF analysis revealed anti-MOG antibodies in only one case. The infection investigations were negative in all cases except positive COVID 19 serology in one caseThe diagnosis retained in our patients were 2 cases of Behcet's disease, 1 monophasic neuritis, 1 optic neuritis with anti-MOG, 1 CRION, 1 case linked to COVID 19 in the absence of another plausible cause. In one case, no diagnosis was retained.Seventy percent of the patients benefited from treatment with corticosteroids pulse, only 2 did not receive treatment, the short-term evolution was favorable in 5 patients with a total recovery of visual acuity, one patient has evolved into atrophy of the left optic nerve and kept visual acuity low to 1/10 of the left eye.The medium-term evolution was marked by recurrence in 3 patients, 5 episodes in the 2 patients with Behcet's disease and 8 episodes in CRION which required the use of immunosuppressive treatment and biotherapy for Behcet's disease and plasmapheresis for CRION.ConclusionDespite the fact that our small series of patients is not representative, we found similar characteristics described in children in other studies. The average onset age was 10 years, with a female predominance, the severe decrease in visual acuity with frequent bilateral involvement. The diagnosis of ON is clinical and must be considered in any sudden drop in visual acuity. The diagnosis of the underlying pathology is often difficult but it’s important in order to propose an adequate specific treatment. The treatment of children's ON is controversial and usually extrapolated from adults. Most practitioners use corticosteroids pulse. The visual prognosis seems good in children, particularly in the case of bilateral involvement, but depends essentially on the aetiology.

Ophthalmologic Microvascular changes in Wolfram syndrome

AbstractPurposeTo evaluate ophthalmic, systemic, genotype features and microvascular abnormalities of patients with Wolfram syndrome (WFS).MethodsCross‐sectional, prospective evaluation of consecutive patients with WFS and healthy subjects. WFS diagnosis was performed based on the clinical presentation and detection of biallelic pathogenic variants in the WFS1 gene. All patients underwent a complete ophthalmological examination and a retinal vasculature evaluation by OCT‐A. Quantitative analysis included: whole‐image vessel density (VD, %), inside disk VD and peripapillary VD of the ONH and peripapillary region, as well as, whole VD for parafoveal superficial capillary plexus (SCP) of the macula.ResultsFifty‐eight eyes were included in this study, 26 eyes from patients with WFS and 32 eyes from healthy subjects. Seven families were included, twelve patients had biallelic pathogenic variants whereas one had one pathogenic variant in the WFS1 gene confirming the diagnosis of WFS type 1 and Wolfram‐like syndrome, respectively. Optic atrophy and diabetes mellitus were the most common systemic findings. The best corrected visual acuity (BCVA) ranged from light perception to 0.1 logMar. Quantitative evaluation demonstrated a significant difference between WFS and healthy subjects on whole‐image VD, inside disk VD, and peripapillary VD (p &lt; 0.001 for all) and SCP perfusion density (p &lt; 0.001). Ganglion cell complex (GCC) and retinal nerve fiber layer (RNFL) thickness have significant decrease in WFS patients with BCVA more than 1 logMar compared to those with less than 1 logMar (p &lt; 0.001 and p = 0.024, respectively).ConclusionsWFS patients had a decreased of vessel density in ONH, peripapillary microvasculature and in macular microvascular networks. Microvasculature changes seem to occur before a severe decrease in visual acuity, and the decreased of the GCC and RNFL thickness.

Cultivated autologous oral mucosal epithelial transplantation

According to the World Health Organization, corneal blindness is the fourth most common cause of blindness and visual impairment worldwide. In Russia, up to 18% of blindness is caused by corneal damage. Limbal stem cell deficiency (LSCD) is one of the causes of corneal blindness and visual impairment due to anterior epithelial replacement with fibrovascular pannus. Bilateral LSCD may develop in patients with aniridia, Steven-Jones syndrome, and severe corneal burns of both eyes, leading to severe decrease in visual acuity in both eyes and, as a consequence, physical disability associated with blindness. In such cases, cell therapy, based on autologous oral epithelial culture as an alternative to allogeneic limbus transplants, is proposed for reconstruction of the anterior corneal epithelium. This new treatment method promotes corneal reepithelization, better visual acuity, reduced nonspecific ocular complaints and improved quality of life of patients. The effectiveness and significant increase in the frequency of transparent engraftment of donor corneas after cell therapy drives huge interest in this topic all over the world. This review presents literature data on the features of histotopography and methods for obtaining a cultured autologous oral mucosal epithelium, on cell markers that are used to identify epithelial cells, and on methods for creating cell grafts for subsequent transplantation to the corneal surface in LSCD patients.

CLINICAL CASE OF SEVERE INTENSIFICATION OF BLOOD FLOW IN THE CONJUNCTIVA OF THE EYEBALL ONE DAY PRIOR TO THE ONSET OF INTERMEDIATE UVEITIS

Purpose: A clinical case is presented of posterior uveitis inapatientwhoreceivedasubconjunctivalinjectionofKenalog. This finding was revealed during the course of adailyassessmentofconjunctivalmicrovascularhemodynamics.Methods:Slitlampbiomicroscopyoftheconjunctivalmicrovasculaturewasperformedbeforeandaftertheemergenceofintermediateuveitisina28-year-oldman.Result: A case of acute vision loss and the occurrence ofintermediate uveitis of the right eye is described in a patientwhopreviouslyreceivedKenalogadministeredsubconjunctivally to treat mild anterior uveitis, which waswithoutvisualimpairment.Dailymonitoringoftheconjunctival microvasculature revealed that the blood flowrate of the right eye considerably increased after Kenalogadministrationthedaybeforepatientvisiondeterioratedand posterioruveitiswithopacityofthevitreousbodyoccurred.The extent of the pronounced intensification ofblood flow wassurprising.Conclusion:The emergence ofacute intermediate uveitisfollowing Kenalog administration was preceded by a severeincrease in bloodcirculation in theconjunctivalvesselsofthe eye, which decreased one day after a severe decrease invisualacuity. It is suggested that this increase in blood flowprecedingpathologymaybeacharacteristicofanyinflammatoryprocessthatoccursinthehumanbody

Raxone dans la neuropathie optique de Leber : retour d’expérience parisienne

Leber's Hereditary Optic Neuropathy (LHON) causes a rapid and severe decrease in visual acuity. Raxone® (Idebenone, Santhera) is the only drug to have a European Marketing Authorization for the treatment of this optic neuropathy. It can be proposed in the first months after the onset of this optic neuropathy, according to an international consensus meeting. Retrospective study of the efficacy of Raxone® on the visual acuity of patients with genetically confirmed LHON who were followed in four Parisian hospitals. The primary endpoint is the best recovery of LogMar visual acuity between baseline and the end of follow-up. The secondary endpoints are the evolution of LogMar visual acuity of the best eye at baseline and change in LogMar visual acuity for each eye considered separately. Seventeen patients, three women and 14men, mean age 34.2years, naive to treatment with Raxone® were included in this study. The mean duration of treatment was 11.0±6.6months. A mitochondrial DNA mutation was found in all patients. Only 2had the 14484 mutation. A recovery of better LogMar visual acuity was found at the end of the treatment for 4eyes (23.5%), and a deterioration was observed for 8 (47.0%). Only 2eyes (11.7%) with the best visual acuity at baseline improved. On the other hand, 17.6% of the eyes considered separately had an improvement in their LogMar visual acuity at the end of the treatment. The results confirm the trend of Raxone® treatment to improve patients' visual acuity. Given the recommendations of a consensus conference, this treatment should be started early after the onset of LHON. It is therefore important to look for this diagnosis in the presence of any hereditary optic neuropathy, in order to be able to initiate this treatment.

Intérêt de l’imagerie multimodale dans le diagnostic de neurorétinopathie maculaire aiguë

Acute macular neuroretinopathy is a retinal disease, usually presenting with a "normal fundus". Thus, this condition can be mistaken for optic neuropathy. Herein we present five clinical cases of patients affected with acute macular neuroretinopathy; one of them is a retrospective diagnosis while the others were diagnosed on initial examination. In the five cases, multimodal imaging with infrared photography and OCT helped to establish the diagnosis. Retrospective study of five clinical cases. Initial and final best visual acuities as well as infrared and OCT imaging were collected for all patients. All patients initially reported a visual disturbance associated with a more or less severe decrease in visual acuity. Infrared imaging showed a dark, perifoveolar appearance of the lesions. In all cases, OCT images showed thickening and hyperreflectivity of the outer plexiform layer, extending towards the outer retinal layers. Acute macular neuroretinopathy is a clinical entity that has been long-described, which now benefits widely from new imaging technologies, allowing an earlier and more accurate diagnosis, but calling into question the actual name of this condition. The exact pathophysiology of the condition remains nonetheless incompletely elucidated.

Two cases of bilateral amiodarone-associated optic neuropathy

The widespread use of amiodarone is limited by its toxicity, notably to the optic nerve. We report two cases of bilateral optic nerve neuropathy due to amiodarone, and provide a detailed description of the disease. The first case was a 59-year-old man complaining from insidious monocular loss of vision within ten months of initiating amiodarone. Funduscopy and optical coherence tomography showed bilateral optic disc edema. The second case was a 72-year-old man presenting with a decrease in visual acuity in his left eye for a month. Funduscopy showed a left optic nerve edema, and fluorescein angiography showed bilateral papillitis. In both cases, the clinical presentation was not suggestive of ischemic neuropathy, because of the preservation of visual acuity and the insidious onset. In addition, both cardiovascular and inflammatory work-up were normal. An amiodarone-associated neuropathy was suspected, and amiodarone was discontinued with the approval of the cardiologist, with complete regression of the papilledema and a stabilization of visual symptoms. Differentiating between amiodarone-associated optic neuropathy and anterior ischemic optic neuropathy may be complicated by the cardiovascular background of such patients. The major criterion is the absence of a severe decrease in visual acuity; other criteria are the normality of cardiovascular and inflammatory work-up, and the improvement or the absence of worsening of symptoms after discontinuation of amiodarone. Amiodarone-associated neuropathy remains a diagnosis of exclusion, and requires amiodarone discontinuation, which can only be done with the approval of a cardiologist, and sometimes requires replacement therapy.

Verteporfin PDT for subfoveal occult CNV in AMD: two-year results of a randomized trial

ABSTRACTObjective: To determine whether verteporfin photodynamic therapy (PDT) can safely reduce the risk of vision loss in patients with subfoveal occult with no classic choroidal neovascularization (CNV) due to age-related macular degeneration.Research design and methods: Eligible patients were ≥50 years of age with lesion size ≤6 disc areas and best-corrected vision 20/40–20/200. A total of 364 patients with occult with no classic CNV were randomly assigned 2 : 1 to verteporfin PDT (n = 244) or placebo (n = 120). The primary outcome measures were loss of ≥15 and ≥30 letters of visual acuity (VA) from baseline at 12 and 24 months.Results: A total of 37% and 47% of verteporfin-treated patients versus 45% and 53% of placebo recipients lost ≥15 letters of VA at month 12 and month 24, respectively; 16% and 23% of verteporfin-treated patients versus 17% and 25% of placebo recipients lost ≥30 letters at month 12 and month 24, respectively. These differences were not statistically significant. Four (1.6%) verteporfin-treated patients and one placebo patient (who received verteporfin in error) experienced an acute severe VA decrease; all five patients recovered some degree of vision. No unexpected ocular or systemic adverse events were identified.Conclusions: Verteporfin PDT in the treatment of occult with no classic CNV was safe and well-tolerated. The differences between the two groups in the primary efficacy variables were not significant. Baseline characteristics and patient selection methods may have contributed to the small treatment effect.Trial registration: ClinicalTrials.gov identifier: NCT00121407.

Verteporfin therapy in occult with no classic CNV due to AMD: results of the Photodynamic Therapy in Occult-Only Lesions study

To provide further information on verteporfin photodynamic therapy in occult with no classic choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). Verteporfin therapy was administered at baseline and then at months 3, 6, and 9, if fluorescein leakage from CNV was evident on angiography. Of 202 patients enrolled, 184 completed 12 months. Each patient was treated in one eye only. All study eyes received verteporfin therapy at baseline, with a progressive decrease in the number treated at subsequent visits (mean 2.5 treatments during 12 months). The mean change in visual acuity letter score from baseline to month 12 was -11.9. At month 12, 164 eyes (82.4%) had lost <30 letters of visual acuity, 123 eyes (61.8%) had lost <15 letters, 78 eyes (39.2%) had lost <5 letters, 31 (15.6%) had >5-letter increase, and 7 (3.5%) had >15-letter improvement. The percentage of eyes with fluorescein leakage from CNV decreased from 75.5% at month 3 to 25.1% at month 12. Adverse events were documented for 54% patients. Few patients had treatment-associated adverse events (7%). Acute severe visual acuity decrease occurred in two eyes (1%), one of which had visual acuity that returned to baseline by the next follow-up visit. This study provides additional evidence that over 12 months, verteporfin is generally well tolerated and maintains or improves visual acuity in over one-third of eyes containing occult-only CNV. Verteporfin also improved anatomical outcomes by reducing leakage from CNV in at least two-thirds of eyes.

Photodynamic therapy for neovascular age-related macular degeneration

In neovascular age-related macular degeneration (AMD) new vessels grow under the retina distorting vision and leading to scarring. This is exacerbated if the blood vessels leak. Photodynamic therapy (PDT) has been investigated as a way to treat the neovascular membranes without affecting the retina. The aim of this review was to examine the effects of PDT in the treatment of neovascular AMD. We searched CENTRAL (Issue 1, 2007), MEDLINE (1966 to March 2007), EMBASE (1980 to March 2007). We contacted experts in the field and searched the reference lists of relevant studies. We included randomised trials of PDT in people with choroidal neovascularisation due to AMD. Two authors independently extracted the data. Risk ratios were combined using a fixed-effect model after testing for heterogeneity. Three published trials were identified that randomised 1022 participants to verteporfin therapy compared to 5% dextrose in water. The TAP and VIP trials were performed by the same investigators using largely the same clinical centres and funded by manufacturers of verteporfin. Outcome data were available at 12 and 24 months after the first treatment. Participants received on average five treatments over two years. The risk ratio of losing three or more lines of visual acuity at 24 months comparing the intervention with the control group was 0.77 (95% confidence interval 0.69 to 0.87). The risk ratio of losing six or more lines of visual acuity at 24 months comparing the intervention with the control group was 0.62 (95% confidence interval 0.50 to 0.76). The results at 12 months were similar to those at 24 months. The most serious adverse outcome, acute (within seven days of treatment) severe visual acuity decrease, occurs in about one in 50 patients. Some outcomes from the more recent VIM trial could be included in the meta-analysis but have not greatly altered the findings. Photodynamic therapy in people with choroidal neovascularisation due to AMD is probably effective in preventing visual loss though there is doubt about the size of the effect. Outcomes and potential adverse effects of this treatment should be monitored closely. Further independent trials of verteporfin are required to establish that the effects seen in this study are consistent and to examine important issues not yet addressed, particularly relating to quality of life and cost. However, the advent of new interventions for AMD make this unlikely.

OCT-3 Study of Serous Retinal Detachment in a Preeclamptic Patient

We report optical coherence tomography-3 (OCT-3) of retinal disorders in acute preeclampsia. A 33-year-old woman developed mind hypertension (170/90 mm Hg) and proteinuria in the 28th week of pregnancy. The patient complained of sudden and severe visual acuity decrease. Fundus exam showed bilateral serous retinal detachment at the macula area. OCT-3 exam demonstrated subretinal and intraretinal fluid. Bilateral serous retinal detachment is an unusual finding of preeclampsia of unknown aetiology. Intense arteriolar vasospasm has been implicated in the pathogenesis of the serous retinal detachment. OCT-3 showed the presence of both subretinal and intraretinal fluid during the acute phase of preeclampsia.

Traumatic Corneal Flap Dislocation One to Six Years After LASIK in Nine Eyes With a Favorable Outcome

To report our experience treating eye trauma after LASIK refractive surgery. Nine eyes of eight patients (one woman and seven men) were treated for ocular trauma: blunt trauma (n=5), sharp instrument trauma (n=2,) and trauma from inflation of automobile air bags during a traffic accident (n=2). The time from LASIK varied between 3 months and 6 years. All patients were hospitalized as a result of severe decrease in visual acuity and pain. Seven of nine LASIK flaps had some degree of dislocation and were lifted, irrigated, and repositioned. Two flaps were edematous without dislocation. Intensive topical steroids and antibiotics were used in all patients up to 3 weeks after trauma. Three months after trauma, five eyes regained their pre-trauma visual acuity (between 20/20 and 20/40), and three eyes lost one line of best spectacle-corrected visual acuity. Trauma occurring several months or years after LASIK may cause flap injury. Adequate and prompt treatment usually is successful.

Complications After Photodynamic Therapy

To evaluate the incidence of complications of photodynamic therapy (PDT) with verteporfin in subfoveal choroidal neovascularizations secondary to age-related macular degeneration and pathologic myopia. In this retrospective interventional case series, the occurrence of complications after PDT in a clinical setting was analyzed. Consecutive medical records of patients with age-related macular degeneration and pathologic myopia treated with PDT were reviewed for complications. Complications included treatment-related systemic adverse events, injection site effects, and ocular adverse events. We included 273 patients (198 with age-related macular degeneration and 75 with pathologic myopia) in the study. A total of 485 photodynamic treatment sessions were performed. Infusion-related back or chest pain was reported by 6 patients (2.2%; 95% confidence interval [CI], 0.8%-4.7%). Injection site effects, extravasation, and photosensitivity reactions were not observed. Dyspnea and flushing during infusion were observed in 2 patients (0.7%; 95% CI, 0.09%-2.6%). Body pain, shortness of breath, and elevated blood pressure were noted in 13 patients (4.8%; 95% CI, 2.6%-8.0%). General pruritus was described by 6 patients (2.2%; 95% CI, 0.8%-4.7%), starting 4 hours after the infusion of verteporfin, and resolved within 72 hours after PDT. A total of 8 patients (2.9%; 95% CI, 1.3%-5.7%) reported an acute severe visual acuity decrease of at least 4 Early Treatment Diabetic Retinopathy Study lines occurring within 7 days of treatment. Complications associated with PDT are uncommon, but there were limitations of retrospective studies for identifying safety problems. Complications like acute severe visual events may occur in about 3% of patients. We believe that this risk is outweighed by the benefits of PDT on visual function in most patients.

Acute severe visual acuity decrease after photodynamic therapy with verteporfin: case reports from randomized clinical trials—TAP and VIP report no. 3*1

Purpose To describe in detail occurrences of acute severe visual acuity decrease after photodynamic therapy (PDT) with verteporfin in the Treatment of Age-related macular degeneration with Photodynamic therapy (TAP) Investigation and the Verteporfin In Photodynamic therapy (VIP) Trial. Design Observational case series. Methods Retrospective review of all cases that developed acute severe visual acuity decrease after treatment. Results Of 15 acute severe visual acuity decrease events originally identified in 14 eyes of 14 patients, one event in one patient was judged unlikely to have been an acute severe visual acuity decrease event on retrospective review of these events in preparation of this report. Eleven events occurred after the first treatment. At follow-up, 10 improved by at least 1 line in visual acuity from the level noted at the time of the event. Of the nine patients returning for the month 24 examination, visual acuity decreased at least 3 lines from baseline in six, including at least 6 lines in four, and remained within 1 line in three. Associated abnormal morphology included three with a serous macular detachment and abnormal choroidal hypofluorescence, four with macular hemorrhage, three with a greenish subfoveal hemorrhage, and four with no abnormality. Events appeared to be more likely when patients had a visual acuity of 20/50 or better. Conclusions Acute severe visual acuity decrease after PDT with verteporfin was an uncommon event; the risk did not outweigh the benefits of therapy previously reported. When considering verteporfin therapy, patients should be warned of the possibility of this serious adverse event.

Acute severe visual acuity decrease after photodynamic therapy with verteporfin: case reports from randomized clinical trials—TAP and VIP report no. 3

Purpose To describe in detail occurrences of acute severe visual acuity decrease after photodynamic therapy (PDT) with verteporfin in the Treatment of Age-related macular degeneration with Photodynamic therapy (TAP) Investigation and the Verteporfin In Photodynamic therapy (VIP) Trial. Design Observational case series. Methods Retrospective review of all cases that developed acute severe visual acuity decrease after treatment. Results Of 15 acute severe visual acuity decrease events originally identified in 14 eyes of 14 patients, one event in one patient was judged unlikely to have been an acute severe visual acuity decrease event on retrospective review of these events in preparation of this report. Eleven events occurred after the first treatment. At follow-up, 10 improved by at least 1 line in visual acuity from the level noted at the time of the event. Of the nine patients returning for the month 24 examination, visual acuity decreased at least 3 lines from baseline in six, including at least 6 lines in four, and remained within 1 line in three. Associated abnormal morphology included three with a serous macular detachment and abnormal choroidal hypofluorescence, four with macular hemorrhage, three with a greenish subfoveal hemorrhage, and four with no abnormality. Events appeared to be more likely when patients had a visual acuity of 20/50 or better. Conclusions Acute severe visual acuity decrease after PDT with verteporfin was an uncommon event; the risk did not outweigh the benefits of therapy previously reported. When considering verteporfin therapy, patients should be warned of the possibility of this serious adverse event.

Large submacular hemorrhages after verteporfin therapy

PurposeTo report the occurrence of large submacular hemorrhages after photodynamic therapy with verteporfin in age-related macular degeneration patients with subfoveal choroidal neovascularization (CNV) composed of occult with no classic CNV in whom the hemorrhage precluded determining if additional therapy should be given within 3 months after initiation of treatment. DesignRetrospective, noncomparative case series. MethodsThe records of all age-related macular degeneration patients who received verteporfin therapy for subfoveal lesions composed of occult with no classic CNV between February and July 2001 at The Wilmer Eye Institute were reviewed. Subjects who reported either having undergone a procedure to remove intraocular blood before a month 3 follow-up visit, or who had submacular hemorrhage at the month 3 visit that was severe enough to preclude determining if additional verteporfin therapy should be given were identified. ResultsFifty-five eyes of 52 patients were reviewed. Five eyes (9% [95% confidence interval, 1.4%–16.6%]) developed submacular hemorrhage that precluded determining if additional verteporfin therapy should be given. Visual acuity 3 months after documentation of the hemorrhage decreased a median of 8.5 lines compared with pretreatment acuity. ConclusionsEven in the absence of acute severe visual acuity decrease, submacular hemorrhage after verteporfin therapy can be associated with severe vision loss and preclude determining if additional therapy should be given.

Verteporfin therapy of subfoveal choroidal neovascularization in age-related macular degeneration: meta-analysis of 2-year safety results in three randomized clinical trials: Treatment Of Age-Related Macular Degeneration With Photodynamic Therapy and Verteporfin In Photodynamic Therapy Study Report no. 4.

We sought to evaluate the detailed safety profile of photodynamic therapy with verteporfin in patients with subfoveal choroidal neovascularization (CNV) caused by age-related macular degeneration (ARMD) from the combined analysis of three multicenter, double-masked, placebo-controlled, randomized 24-month clinical trials of similar design (TAP Investigation Studies A and B and the VIP ARMD Trial), and to clarify the adverse reaction information in the current verteporfin product prescription information approved in the United States. Nine hundred forty-eight patients were randomly assigned to verteporfin or placebo. Treatment was administered as described in previous reports. All general entry criteria were similar, so systemic safety results were combined for this analysis. Entry criteria for CNV lesion composition and visual acuity in the two TAP Investigation trials was different from those used in the VIP ARMD trial, so ocular safety results for the treated eye were not combined. The percentage of patients who experienced at least one ocular or nonocular adverse event, regardless of relationship to therapy, was similar between the verteporfin and placebo groups (92.3 and 89.1%, respectively, P = 0.114). The overall incidence of study eye adverse events was not significantly different between verteporfin and placebo. The only clinically relevant ocular adverse events reported with higher incidence after verteporfin compared with placebo were visual disturbances (22.1 versus 15.5% in TAP [P = 0.054] and 41.7 and 22.8% in VIP [P < 0.001]). Acute severe visual acuity decrease (defined as a visual acuity letter score decrease of at least 20, equivalent to at least four-line decrease, within 7 days of therapy) occurred in 3 patients treated with verteporfin in the TAP Investigation (0.7%) and 11 in the VIP ARMD trial (4.9%). Systemic adverse events with increased incidence after verteporfin compared with placebo, most of which were transient and mild or moderate, were injection site reactions (13.1 versus 5.6%; P < 0.001), photosensitivity reactions (2.4 versus 0.3%; P = 0.016), and infusion-related back pain (2.4 versus 0%; P = 0.004). No clinically relevant difference was observed between the verteporfin and placebo groups in any other adverse event. In 948 ARMD patients, verteporfin therapy had an overall safety profile similar to that for placebo, with a few exceptions. Visual disturbances, including acute severe visual acuity decrease, did not affect the net vision outcome benefits associated with treatment that has been reported previously. This detailed safety profile of verteporfin therapy clarifies the adverse reaction information in the current verteporfin product prescription information.